Updated on 2026/05/26

写真a

 
YAMAGUCHI YUKI
 
Organization
School of Life Science and Technology Professor
Title
Professor
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News & Topics

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Degree

  • Ph.D. ( Tokyo Institute of Technology )

Research Areas

  • Life Science / Functional biochemistry

  • Life Science / Molecular biology

  • Life Science / Cell biology

Education

  • Tokyo Institute of Technology   Graduate School of Bioscience and Biotechnology   Department of Biotechnology

    1995.4 - 1999.3

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    Country: Japan

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  • Tokyo Institute of Technology   School of Bioscience and Biotechnology

    - 1995

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    Country: Japan

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Research History

  • Tokyo Institute of Technology   School of Life Science and Technology   Professor

    2016.4

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  • Tokyo Medical University   Chemical Biology Laboratory   Visiting Professor

    2014.10 - 2022.3

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  • Tokyo Institute of Technology   Graduate School of Bioscience and Biotechnology   Professor

    2013.7 - 2016.3

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  • Japan Science and Technology Agency   PRESTO   Researcher

    2010.10 - 2014.3

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  • Tokyo Institute of Technology   Graduate School of Bioscience and Biotechnology   Associate Professor

    2009.1 - 2013.6

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  • Tokyo Institute of Technology   Graduate School of Bioscience and Biotechnology   Assistant Professor

    2007.4 - 2008.12

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  • Tokyo Institute of Technology   Graduate School of Bioscience and Biotechnology   Assistant Professor

    2002.1 - 2007.3

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  • Japan Science and Technology Agency   PRESTO   Researcher

    2001.12 - 2005.3

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  • The Research Association for Biotechnology   Research Fellow

    2001.4 - 2001.11

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  • Japan Society for the Promotion of Science   Research Fellow

    1999.1 - 2001.3

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Professional Memberships

Papers

  • Multiple structures of RNA polymerase II isolated from human nuclei by ChIP-CryoEM analysis Reviewed International journal

    Tomoya Kujirai, Junko Kato, Kyoka Yamamoto, Seiya Hirai, Takeru Fujii, Kazumitsu Maehara, Akihito Harada, Lumi Negishi, Mitsuo Ogasawara, Yuki Yamaguchi, Yasuyuki Ohkawa, Yoshimasa Takizawa, Hitoshi Kurumizaka

    Nature Communications   16 ( 1 )   4724 - 4724   2025.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-025-59580-x

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  • INTS15, A Subunit of the Integrator Complex, Plays a Key Regulatory Role in Cell Cycle and Differentiation Reviewed International journal

    Noriyuki Azuma, Yuki Yamaguchi, Taku Tanaka, Emiko Matsuzaka, Yuki Saida, Tadashi Yokoi, Hiroshi Handa, Jun Hirayama, Hiroshi Nishina

    Genes to Cells   30 ( 3 )   e70015 - e70015   2025.5

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/gtc.70015

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  • Multi-omics analysis using antibody-based in situ biotinylation technique suggests the mechanism of Cajal body formation. Reviewed International journal

    Keisuke Noguchi, Hidefumi Suzuki, Ryota Abe, Keiko Horiuchi, Rena Onoguchi-Mizutani, Nobuyoshi Akimitsu, Shintaro Ogawa, Tomohiko Akiyama, Yoko Ike, Yoko Ino, Yayoi Kimura, Akihide Ryo, Hiroshi Doi, Fumiaki Tanaka, Yutaka Suzuki, Atsushi Toyoda, Yuki Yamaguchi, Hidehisa Takahashi

    Cell reports   43 ( 9 )   114734 - 114734   2024.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    Membrane-less subcellular compartments play important roles in various cellular functions. Although techniques exist to identify components of cellular bodies, a comprehensive method for analyzing both static and dynamic states has not been established. Here, we apply an antibody-based in situ biotinylation proximity-labeling technique to identify components of static and dynamic nuclear bodies. Using this approach, we comprehensively identify DNA, RNA, and protein components of Cajal bodies (CBs) and then clarify their interactome. By inhibiting transcription, we capture dynamic changes in CBs. Our analysis reveals that nascent small nuclear RNAs (snRNAs) transcribed in CBs contribute to CB formation by assembling RNA-binding proteins, including frontotemporal dementia-related proteins, RNA-binding motif proteins, and heterogeneous nuclear ribonucleoproteins.

    DOI: 10.1016/j.celrep.2024.114734

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  • ZNF276 and WIZ are CRBN neosubstrates involved in the anti-angiogenic activity of thalidomide and immunomodulatory drugs

    Takumi Ito, Tomoko Asatsuma-Okumura, Akinori Endo, Junichi Yamamoto, Yoshiko Iwai, Yuki Yamaguchi, Mikihiko Naito, Hiroshi Handa, Yasushi Saeki

    2023.11

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    Publisher:Research Square Platform LLC  

    Abstract

    Thalidomide was once developed as a sedative but had been withdrawn from the market in the 1960s because of its serious teratogenicity. Currently, this drug is reevaluated and used for the treatment of multiple myeloma, and many derivatives such as lenalidomide and pomalidomide have been developed. CRBN is a primary target of thalidomide and its derivatives and forms an E3 ubiquitin ligase complex with DDB1 and CUL4. Although the basic mechanism of action of thalidomide is quite well understood, a long-standing question remains regarding its inhibitory effect on angiogenesis. Here, we employed a comprehensive proteomic approach using thalidomide-treated endothelial cells to identify ZNF276 and WIZ as CRBN neosubstrates. Thalidomide and its derivatives exert their anti-angiogenic effects through these two zinc finger proteins, resulting in the downregulation of FABP4. This study reveals the CRBN neosubstrates involved in thalidomide-induced anti-angiogenesis and provides attractive therapeutic targets of CRBN-based protein degraders.

    DOI: 10.21203/rs.3.rs-3510134/v1

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    Other Link: https://www.researchsquare.com/article/rs-3510134/v1.html

  • Integrator complex subunit 15 controls mRNA splicing and is critical for eye development Reviewed

    Noriyuki Azuma, Tadashi Yokoi, Taku Tanaka, Emiko Matsuzaka, Yuki Saida, Sachiko Nishina, Miho Terao, Shuji Takada, Maki Fukami, Kohji Okamura, Kayoko Maehara, Tokiwa Yamasaki, Jun Hirayama, Hiroshi Nishina, Hiroshi Handa, Yuki Yamaguchi

    Human Molecular Genetics   2023.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    Abstract

    The eye and brain are composed of elaborately organized tissues, development of which is supported by spatiotemporally precise expression of a number of transcription factors and developmental regulators. Here we report the molecular and genetic characterization of Integrator complex subunit 15 (INTS15). INTS15 was identified in search for the causative gene(s) for an autosomal-dominant eye disease with variable individual manifestation found in a large pedigree. While homozygous Ints15 knockout mice are embryonic lethal, mutant mice lacking a small C-terminal region of Ints15 show ocular malformations similar to the human patients. INTS15 is highly expressed in the eye and brain during embryogenesis and stably interacts with the Integrator complex to support snRNA 3′ end processing. Its knockdown resulted in missplicing of a large number of genes, probably as a secondary consequence, and substantially affected genes associated with eye and brain development. Moreover, studies using human iPS-derived neural progenitor cells showed that INTS15 is critical for axonal outgrowth in retinal ganglion cells. This study suggests a new link between general transcription machinery and a highly specific hereditary disease.

    DOI: 10.1093/hmg/ddad034

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  • Discovery of CRBN as a target of thalidomide: a breakthrough for progress in the development of protein degraders Invited Reviewed

    Junichi Yamamoto, Takumi Ito, Yuki Yamaguchi, Hiroshi Handa

    Chemical Society Reviews   51 ( 15 )   6234 - 6250   2022.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Royal Society of Chemistry (RSC)  

    Thalidomide and its derivatives are the only protein degraders currently used in clinical practice. This tutorial review provides an overview of the mechanism of action of thalidomide-based degraders and their future perspectives.

    DOI: 10.1039/d2cs00116k

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  • The 3' Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies' association with histone locus bodies. International journal

    Hidefumi Suzuki, Ryota Abe, Miho Shimada, Tomonori Hirose, Hiroko Hirose, Keisuke Noguchi, Yoko Ike, Nanami Yasui, Kazuki Furugori, Yuki Yamaguchi, Atsushi Toyoda, Yutaka Suzuki, Tatsuro Yamamoto, Noriko Saitoh, Shigeo Sato, Chieri Tomomori-Sato, Ronald C Conaway, Joan W Conaway, Hidehisa Takahashi

    Nature communications   13 ( 1 )   2905 - 2905   2022.5

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    Non-polyadenylated mRNAs of replication-dependent histones (RDHs) are synthesized by RNA polymerase II (Pol II) at histone locus bodies (HLBs). HLBs frequently associate with Cajal bodies (CBs), in which 3'-end processing factors for RDH genes are enriched; however, this association's role in transcription termination of RDH genes remains unclear. Here, we show that Pol II pauses immediately upstream of transcript end sites of RDH genes and Mediator plays a role in this Pol II pausing through CBs' association with HLBs. Disruption of the Mediator docking site for Little elongation complex (LEC)-Cap binding complex (CBC)-Negative elongation factor (NELF), components of CBs, interferes with CBs' association with HLBs and 3' Pol II pausing, resulting in increased aberrant unprocessed RDH gene transcripts. Our findings suggest Mediator's involvement in CBs' association with HLBs to facilitate 3' Pol II pausing and subsequent 3'-end processing of RDH genes by supplying 3'-end processing factors.

    DOI: 10.1038/s41467-022-30632-w

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  • PLZF and its fusion proteins are pomalidomide-dependent CRBN neosubstrates Reviewed

    Nobuyuki Shimizu, Tomoko Asatsuma-Okumura, Junichi Yamamoto, Yuki Yamaguchi, Hiroshi Handa, Takumi Ito

    Communications Biology   4 ( 1 )   2021.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>Pomalidomide and lenalidomide are immunomodulatory agents that were derived from thalidomide. Cereblon (CRBN) is a common direct target of thalidomide and related compounds and works as a Cullin Ring 4 E3 ubiquitin ligase (CRL4) with DDB1, CUL4, and ROC1. The substrate specificity of CRL4CRBN is modulated by thalidomide-related compounds. While lenalidomide is approved for the treatment of several diseases including multiple myeloma, 5q- syndrome, mantle cell lymphoma, and follicular lymphoma, pomalidomide is approved only for the treatment of lenalidomide-resistant multiple myeloma. Here we show that PLZF/ZBTB16 and its fusion proteins are pomalidomide-dependent neosubstrates of CRL4CRBN. <italic>PLZF</italic> joins to <italic>RARα</italic> or potentially other partner genes, and the translocation causes leukemias, such as acute promyelocytic leukemia and T-cell acute lymphoblastic leukemia. We demonstrate that pomalidomide treatment induces PLZF-RARα degradation, resulting in antiproliferation of leukemic cells expressing PLZF-RARα. This study highlights a potential therapeutic role of pomalidomide as a degrader of leukemogenic fusion proteins.

    DOI: 10.1038/s42003-021-02801-y

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    Other Link: https://www.nature.com/articles/s42003-021-02801-y

  • Three human RNA polymerases interact with TFIIH via a common RPB6 subunit

    Masahiko Okuda, Tetsufumi Suwa, Hidefumi Suzuki, Yuki Yamaguchi, Yoshifumi Nishimura

    Nucleic Acids Research   2021.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    <title>Abstract</title>
    In eukaryotes, three RNA polymerases (RNAPs) play essential roles in the synthesis of various types of RNA: namely, RNAPI for rRNA; RNAPII for mRNA and most snRNAs; and RNAPIII for tRNA and other small RNAs. All three RNAPs possess a short flexible tail derived from their common subunit RPB6. However, the function of this shared N-terminal tail (NTT) is not clear. Here we show that NTT interacts with the PH domain (PH-D) of the p62 subunit of the general transcription/repair factor TFIIH, and present the structures of RPB6 unbound and bound to PH-D by nuclear magnetic resonance (NMR). Using available cryo-EM structures, we modelled the activated elongation complex of RNAPII bound to TFIIH. We also provide evidence that the recruitment of TFIIH to transcription sites through the p62–RPB6 interaction is a common mechanism for transcription-coupled nucleotide excision repair (TC-NER) of RNAPI- and RNAPII-transcribed genes. Moreover, point mutations in the RPB6 NTT cause a significant reduction in transcription of RNAPI-, RNAPII- and RNAPIII-transcribed genes. These and other results show that the p62–RPB6 interaction plays multiple roles in transcription, TC-NER, and cell proliferation, suggesting that TFIIH is engaged in all RNAP systems.

    DOI: 10.1093/nar/gkab612

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  • Exploiting ubiquitin ligase cereblon as a target for small-molecule compounds in medicine and chemical biology

    Takumi Ito, Yuki Yamaguchi, Hiroshi Handa

    Cell Chemical Biology   28 ( 7 )   987 - 999   2021.5

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.chembiol.2021.04.012

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  • ARID2 is a pomalidomide-dependent CRL4CRBN substrate in multiple myeloma cells. Reviewed International journal

    Junichi Yamamoto, Tetsufumi Suwa, Yuki Murase, Shumpei Tateno, Hirotaka Mizutome, Tomoko Asatsuma-Okumura, Nobuyuki Shimizu, Tsutomu Kishi, Shuji Momose, Masahiro Kizaki, Takumi Ito, Yuki Yamaguchi, Hiroshi Handa

    Nature chemical biology   16 ( 11 )   1208 - 1217   2020.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media {LLC}  

    The immunomodulatory drug (IMiD) thalidomide and its derivatives lenalidomide and pomalidomide are therapeutic agents used in the treatment of multiple myeloma. Although pomalidomide offers considerable clinical benefits to patients with lenalidomide-resistant multiple myeloma, the molecular mechanisms underlying its superior efficacy remain unclear. Here we show that ARID2, a component of the polybromo-associated BAF (PBAF) chromatin-remodeling complex, is a pomalidomide-induced neosubstrate of CRL4CRBN. BRD7, another subunit of PBAF, is critical for pomalidomide-induced ARID2 degradation. ARID2 is involved in transcriptional regulation of pomalidomide target genes including MYC. Pomalidomide is more effective than lenalidomide in degrading ARID2 and is capable of inhibiting MYC expression and proliferation in lenalidomide-resistant cell lines. Notably, ARID2 expression is associated with a poor prognosis and is higher in chemoresistant minimal residual disease (MRD) populations, and in patients with relapsed/refractory multiple myeloma. These findings suggest that ARID2 is a promising target for overcoming lenalidomide resistance in patients with multiple myeloma.

    DOI: 10.1038/s41589-020-0645-3

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  • サリドマイド胎芽症診療ガイド 2020

    山口 雄輝

    サリドマイド胎芽症診療ガイド 2020   2020.5

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    Language:Japanese   Publisher:国立国際医療研究センター  

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  • Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide. Reviewed International journal

    Shumpei Tateno, Midori Iida, Satoshi Fujii, Tetsufumi Suwa, Miki Katayama, Haruka Tokuyama, Junichi Yamamoto, Takumi Ito, Satoshi Sakamoto, Hiroshi Handa, Yuki Yamaguchi

    Scientific reports   10 ( 1 )   4012 - 4012   2020.3

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    Pomalidomide, a derivative of thalidomide, is an effective treatment for multiple myeloma. The drug exerts its effects through CRBN, a component of the E3 ubiquitin ligase complex CRL4CRBN. To search for novel factors involved in the anti-cancer activity of pomalidomide, we performed a genome-wide shRNA library screen and identified 445 genes as those affecting pomalidomide sensitivity. Genes encoding components of the ubiquitin-proteasome pathway, such as subunits of the CRL4CRBN complex, the COP9 signalosome, and the 26S proteasome, were among the pomalidomide-affecting genes. Karyopherin beta 1 (KPNB1) was identified as a novel pomalidomide-affecting gene. KPNB1 was required for the nuclear import of CRBN and for the CRBN-directed, pomalidomide-dependent degradation of a clinically relevant substrate, the transcription factor Aiolos. By contrast, the cytoplasmic translation factor GSPT1 was degraded following treatment with the thalidomide derivative CC-885 only when CRBN was present in the cytoplasm, indicating that subcellular distribution of CRBN is critical for the efficacy of thalidomide-based medications.

    DOI: 10.1038/s41598-020-61027-w

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  • The role of Mediator and Little Elongation Complex in transcription termination. Reviewed International journal

    Hidehisa Takahashi, Amol Ranjan, Shiyuan Chen, Hidefumi Suzuki, Mio Shibata, Tomonori Hirose, Hiroko Hirose, Kazunori Sasaki, Ryota Abe, Kai Chen, Yanfeng He, Ying Zhang, Ichigaku Takigawa, Tadasuke Tsukiyama, Masashi Watanabe, Satoshi Fujii, Midori Iida, Junichi Yamamoto, Yuki Yamaguchi, Yutaka Suzuki, Masaki Matsumoto, Keiichi I Nakayama, Michael P Washburn, Anita Saraf, Laurence Florens, Shigeo Sato, Chieri Tomomori-Sato, Ronald C Conaway, Joan W Conaway, Shigetsugu Hatakeyama

    Nature communications   11 ( 1 )   1063 - 1063   2020.2

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    Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3' end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.

    DOI: 10.1038/s41467-020-14849-1

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  • p63 is a cereblon substrate involved in thalidomide teratogenicity. Reviewed International journal

    Tomoko Asatsuma-Okumura, Hideki Ando, Marco De Simone, Junichi Yamamoto, Tomomi Sato, Nobuyuki Shimizu, Kazuhide Asakawa, Yuki Yamaguchi, Takumi Ito, Luisa Guerrini, Hiroshi Handa

    Nature chemical biology   15 ( 11 )   1077 - 1084   2019.11

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    Cereblon (CRBN) is a primary target of thalidomide and mediates its multiple pharmacological activities, including teratogenic and antimyeloma activities. CRBN functions as a substrate receptor of the E3 ubiquitin ligase CRL4, whose substrate specificity is modulated by thalidomide and its analogs. Although a number of CRL4CRBN substrates have recently been identified, the substrate involved in thalidomide teratogenicity is unclear. Here we show that p63 isoforms are thalidomide-dependent CRL4CRBN neosubstrates that are responsible, at least in part, for its teratogenic effects. The p53 family member p63 is associated with multiple developmental processes. ∆Np63α is essential for limb development, while TAp63α is important for cochlea development and hearing. Using a zebrafish model, we demonstrate that thalidomide exerts its teratogenic effects on pectoral fins and otic vesicles by inducing the degradation of ∆Np63α and TAp63α, respectively. These results may contribute to the invention of new thalidomide analogs lacking teratogenic activity.

    DOI: 10.1038/s41589-019-0366-7

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  • Cereblon Control of Zebrafish Brain Size by Regulation of Neural Stem Cell Proliferation. Reviewed International journal

    Hideki Ando, Tomomi Sato, Takumi Ito, Junichi Yamamoto, Satoshi Sakamoto, Nobuhiro Nitta, Tomoko Asatsuma-Okumura, Nobuyuki Shimizu, Ryota Mizushima, Ichio Aoki, Takeshi Imai, Yuki Yamaguchi, Arnold J Berk, Hiroshi Handa

    iScience   15   95 - 108   2019.5

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    Thalidomide is a teratogen that causes multiple malformations in the developing baby through its interaction with cereblon (CRBN), a substrate receptor subunit of the CRL4 E3 ubiquitin ligase complex. CRBN was originally reported as a gene associated with autosomal recessive non-syndromic mild mental retardation. However, the function of CRBN during brain development remains largely unknown. Here we demonstrate that CRBN promotes brain development by facilitating the proliferation of neural stem cells (NSCs). Knockdown of CRBN in zebrafish embryos impaired brain development and led to small brains, as did treatment with thalidomide. By contrast, overexpression of CRBN resulted in enlarged brains, leading to the expansion of NSC regions and increased cell proliferation in the early brain field and an expanded expression of brain region-specific genes and neural and glial marker genes. These results demonstrate that CRBN functions in the determination of brain size by regulating the proliferation of NSCs during development.

    DOI: 10.1016/j.isci.2019.04.007

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  • Application of high-performance magnetic nanobeads to biological sensing devices. Reviewed International journal

    Kabe Y, Sakamoto S, Hatakeyama M, Yamaguchi Y, Suematsu M, Itonaga M, Handa H

    Analytical and bioanalytical chemistry   411 ( 9 )   1825 - 1837   2019.3

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    Nanomaterials have extensive applications in the life sciences and in clinical diagnosis. We have developed magnetic nanoparticles with high dispersibility and extremely low nonspecific binding to biomolecules and have demonstrated their application in chemical biology (e.g., for the screening of drug receptor proteins). Recently, the excellent properties of nanobeads have made possible the development of novel rapid immunoassay systems and high-precision technologies for exosome detection. For immunoassays, we developed a technology to encapsulate a fluorescent substance in magnetic nanobeads. The fluorescent nanobeads allow the rapid detection of a specific antigen in solution or in tissue specimens. Exosomes, which are released into the blood, are expected to become markers for several diseases, including cancer, but techniques for measuring the absolute quantity of exosomes in biological fluids are lacking. By integrating magnetic nanobead technology with an optical disc system, we developed a novel method for precisely quantifying exosomes in human serum with high sensitivity and high linearity without requiring enrichment procedures. This review focuses on the properties of our magnetic nanobeads, the development of novel biosensors using these nanobeads, and their broad practical applications. Graphical abstract ᅟ.

    DOI: 10.1007/s00216-018-1548-y

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  • TLP-mediated global transcriptional repression after double-strand DNA breaks slows down DNA repair and induces apoptosis. Reviewed International journal

    Suzuki H, Okamoto-Katsuyama M, Suwa T, Maeda R, Tamura TA, Yamaguchi Y

    Scientific reports   9 ( 1 )   4868 - 4868   2019.3

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    Transcription and DNA damage repair act in a coordinated manner. Recent studies have shown that double-strand DNA breaks (DSBs) are repaired in a transcription-coupled manner. Active transcription results in a faster recruitment of DSB repair factors and expedites DNA repair. On the other hand, transcription is repressed by DNA damage through multiple mechanisms. We previously reported that TLP, a TATA box-binding protein (TBP) family member that functions as a transcriptional regulator, is also involved in DNA damage-induced apoptosis. However, the mechanism by which TLP affects DNA damage response was largely unknown. Here we show that TLP-mediated global transcriptional repression after DSBs is crucial for apoptosis induction by DNA-damaging agents such as etoposide and doxorubicin. Compared to control cells, TLP-knockdown cells were resistant to etoposide-induced apoptosis and exhibited an elevated level of global transcription after etoposide exposure. DSBs were efficiently removed in transcriptionally hyperactive TLP-knockdown cells. However, forced transcriptional shutdown using transcriptional inhibitors α-amanitin and 5,6-dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB) slowed down DSB repair and resensitized TLP-knockdown cells to etoposide. Taken together, these results indicate that TLP is a critical determinant as to how cells respond to DSBs and triggers apoptosis to cells that have sustained DNA damage.

    DOI: 10.1038/s41598-019-41057-9

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  • Structural basis of thalidomide enantiomer binding to cereblon Reviewed

    Tomoyuki Mori, Takumi Ito, Shujie Liu, Hideki Ando, Satoshi Sakamoto, Yuki Yamaguchi, Etsuko Tokunaga, Norio Shibata, Hiroshi Handa, Toshio Hakoshima

    Scientific Reports   8 ( 1 )   1294   2018.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nature Publishing Group  

    DOI: 10.1038/s41598-018-19202-7

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  • 遺伝子発現制御機構 クロマチン,転写制御,エピジェネティクス

    田村隆明, 浦聖恵, 山口雄輝

    2017.4

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    Language:Japanese   Publisher:遺伝子発現制御機構 クロマチン,転写制御,エピジェネティクス  

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  • Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance Reviewed

    Yasuaki Kabe, Takanori Nakane, Ikko Koike, Tatsuya Yamamoto, Yuki Sugiura, Erisa Harada, Kenji Sugase, Tatsuro Shimamura, Mitsuyo Ohmura, Kazumi Muraoka, Ayumi Yamamoto, Takeshi Uchida, So Iwata, Yuki Yamaguchi, Elena Krayukhina, Masanori Noda, Hiroshi Handa, Koichiro Ishimori, Susumu Uchiyama, Takuya Kobayashi, Makoto Suematsu

    NATURE COMMUNICATIONS   7   11030   2016.3

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    DOI: 10.1038/ncomms11030

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  • CTCF regulates NELF, DSIF and P-TEFb recruitment during transcription Reviewed

    Clélia Laitem, Justyna Zaborowska, Michael Tellier, Yuki Yamaguchi, Qingfu Cao, Sylvain Egloff, Hiroshi Handa, Shona Murphy

    Transcription   6 ( 5 )   79 - 90   2015.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Taylor and Francis Inc.  

    DOI: 10.1080/21541264.2015.1095269

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  • Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex (vol 35, pg 3459, 2015)

    Qing-Fu Cao, Junichi Yamamoto, Tomoyasu Isobe, Shumpei Tateno, Yuki Murase, Yexi Chen, Hiroshi Handa, Yuki Yamaguchi

    MOLECULAR AND CELLULAR BIOLOGY   35 ( 20 )   4093 - 4093   2015.10

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  • Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex Reviewed

    Qing-Fu Cao, Junichi Yamamoto, Tomoyasu Isobe, Shumpei Tateno, Yuki Murase, Yexi Chen, Hiroshi Handa, Yuki Yamaguchi

    MOLECULAR AND CELLULAR BIOLOGY   35 ( 20 )   3459 - 3470   2015.10

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    DOI: 10.1128/MCB.00601-15

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  • SV40 VP1 major capsid protein in its self-assembled form allows VP1 pentamers to coat various types of artificial beads in vitro regardless of their sizes and shapes Reviewed

    Masaaki Kawano, Koji Doi, Hajime Fukuda, Yoshinori Kita, Kensuke Imai, Takamasa Inoue, Teruya Enomoto, Masanori Matsui, Mamoru Hatakeyama, Yuki Yamaguchi, Hiroshi Handa

    Biotechnology Reports   5 ( 1 )   105 - 111   2015.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier B.V.  

    DOI: 10.1016/j.btre.2014.12.008

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  • Correction to Characterization of the human transcription elongation factor Rtf1: Evidence for nonoverlapping functions of Rtf1 and the Paf1 complex. [Mol Cell Biol, 35, 20, 2015, 3459-3470] Reviewed

    Qing-Fu Cao, Junichi Yamamoto, Tomoyasu Isobe, Shumpei Tateno, Yuki Murase, Yexi Chen, Hiroshi Handa, Yuki Yamaguchi

    Molecular and Cellular Biology   35 ( 23 )   4093   2015

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    DOI: 10.1128/MCB.00914-15

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  • 理系英会話アクティブラーニング2 テツヤ、ディスカッションしようか

    Kyota Ko, Simon Gillett, 近藤 科江, 山口 雄輝

    2014.11

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  • 理系英会話アクティブラーニング1 テツヤ、国際学会いってらっしゃい

    Kyota Ko, Simon Gillett, 近藤 科江, 山口 雄輝

    2014.11

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  • 基礎からしっかり学ぶ生化学

    山口雄輝, 成田央

    2014.10

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  • 新しい遺伝子工学 新版

    半田宏, 山口雄輝

    2014.9

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  • DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes Reviewed

    Junichi Yamamoto, Yuri Hagiwara, Kunitoshi Chiba, Tomoyasu Isobe, Takashi Narita, Hiroshi Handa, Yuki Yamaguchi

    NATURE COMMUNICATIONS   5   4263   2014.6

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  • Magnetically Promoted Rapid Immunoreactions Using Functionalized Fluorescent Magnetic Beads: A Proof of Principle Reviewed

    Satoshi Sakamoto, Kenshi Omagari, Yoshinori Kita, Yusuke Mochizuki, Yasuyuki Naito, Shintaro Kawata, Sachiko Matsuda, Osamu Itano, Hiromitsu Jinno, Hiroya Takeuchi, Yuki Yamaguchi, Yuko Kitagawa, Hiroshi Handa

    CLINICAL CHEMISTRY   60 ( 4 )   610 - 620   2014.4

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    DOI: 10.1373/clinchem.2013.211433

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  • Inhibition of protein SUMOylation by davidiin, an ellagitannin from Davidia involucrata Reviewed

    Misao Takemoto, Yumi Kawamura, Mikako Hirohama, Yuki Yamaguchi, Hiroshi Handa, Hisato Saitoh, Yoichi Nakao, Manabu Kawada, Khan Khalid, Hiroyuki Koshino, Ken-ichi Kimura, Akihiro Ito, Minoru Yoshida

    JOURNAL OF ANTIBIOTICS   67 ( 4 )   335 - 338   2014.4

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  • Salicylic Acid Induces Mitochondrial Injury by Inhibiting Ferrochelatase Heme Biosynthesis Activity Reviewed

    Vipul Gupta, Shujie Liu, Hideki Ando, Ryohei Ishii, Shumpei Tateno, Yuki Kaneko, Masato Yugami, Satoshi Sakamoto, Yuki Yamaguchi, Osamu Nureki, Hiroshi Handa

    MOLECULAR PHARMACOLOGY   84 ( 6 )   824 - 833   2013.12

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    DOI: 10.1124/mol.113.087940

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  • Activation-induced cytidine deaminase auto-activates and triggers aberrant gene expression Reviewed

    Tomoyasu Isobe, Soken-Nakazawa J. Song, Prabha Tiwari, Hiroki Ito, Yuki Yamaguchi, Kazuyuki Yoshizaki

    FEBS LETTERS   587 ( 16 )   2487 - 2492   2013.8

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    DOI: 10.1016/j.febslet.2013.06.028

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  • Viral protein-coating of magnetic nanoparticles using simian virus 40 VP1 Reviewed

    Teruya Enomoto, Masaaki Kawano, Hajime Fukuda, Wataru Sawada, Takamasa Inoue, Kok Chee Haw, Yoshinori Kita, Satoshi Sakamoto, Yuki Yamaguchi, Takeshi Imai, Mamoru Hatakeyama, Shigeyoshi Saito, Adarsh Sandhu, Masanori Matsui, Ichio Aoki, Hiroshi Handa

    JOURNAL OF BIOTECHNOLOGY   167 ( 1 )   8 - 15   2013.8

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    DOI: 10.1016/j.jbiotec.2013.06.005

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  • Systematic Identification of Proteins Binding to Chromatin-Embedded Ubiquitylated H2B Reveals Recruitment of SWI/SNF to Regulate Transcription Reviewed

    Efrat Shema-Yaacoby, Miroslav Nikolov, Mahmood Haj-Yahya, Peter Siman, Eric Allemand, Yuki Yamaguchi, Christian Muchardt, Henning Urlaub, Ashraf Brik, Moshe Oren, Wolfgang Fischle

    CELL REPORTS   4 ( 3 )   601 - 608   2013.8

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    DOI: 10.1016/j.celrep.2013.07.014

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  • Vesnarinone suppresses TNFa mRNA expression by inhibiting valosin-containing protein Reviewed

    Kentaro Hotta, Akihiro Nashimoto, Eiji Yasumura, Masafumi Suzuki, Motoki Azuma, Yosuke Iizumi, Daisuke Shima, Ryusuke Nabeshima, Masaki Hiramoto, Akira Okada, Kumiko Sakata-Sogawa, Makio Tokunaga, Takumi Ito, Hideki Ando, Satoshi Sakamoto, Yasuaki Kabe, Shinichi Aizawa, Takeshi Imai, Yuki Yamaguchi, Hajime Watanabe, Hiroshi Handa

    Molecular Pharmacology   83 ( 5 )   930 - 938   2013.5

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    DOI: 10.1124/mol.112.081935

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  • Systematic changes to the apparent diffusion tensor of in vivo rat brain measured with an oscillating-gradient spin-echo sequence Reviewed

    Jeff Kershaw, Christoph Leuze, Ichio Aoki, Takayuki Obata, Iwao Kanno, Hiroshi Ito, Yuki Yamaguchi, Hiroshi Handa

    NEUROIMAGE   70   10 - 20   2013.4

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    DOI: 10.1016/j.neuroimage.2012.12.036

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  • Vitamin K2 Covalently Binds to Bak and Induces Bak-Mediated Apoptosis Reviewed

    Satoki Karasawa, Motoki Azuma, Takeshi Kasama, Satoshi Sakamoto, Yasuaki Kabe, Takeshi Imai, Yuki Yamaguchi, Keisuke Miyazawa, Hiroshi Handa

    MOLECULAR PHARMACOLOGY   83 ( 3 )   613 - 620   2013.3

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    DOI: 10.1124/mol.112.082602

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  • Transcription elongation factors DSIF and NELF: Promoter-proximal pausing and beyond

    Yuki Yamaguchi, Hirotaka Shibata, Hiroshi Handa

    BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS   1829 ( 1 )   98 - 104   2013.1

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  • Transcription elongation factors DSIF and NELF: promoter-proximal pausing and beyond. Reviewed

    Yamaguchi Y, Shibata H, Handa H

    Biochimica et biophysica acta   1829 ( 1 )   98 - 104   2013.1

  • Identification of DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs) as a Novel Target of Bisphenol A Reviewed

    Yuki Ito, Takumi Ito, Satoki Karasawa, Teruya Enomoto, Akihiro Nashimoto, Yasuyoshi Hase, Satoshi Sakamoto, Tsuneyo Mimori, Yoshihisa Matsumoto, Yuki Yamaguchi, Hiroshi Handa

    PLOS ONE   7 ( 12 )   e50481   2012.12

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  • DSIF Restricts NF-kappa B Signaling by Coordinating Elongation with mRNA Processing of Negative Feedback Genes Reviewed

    Gil Diamant, Liat Amir-Zilberstein, Yuki Yamaguchi, Hiroshi Handa, Rivka Dikstein

    CELL REPORTS   2 ( 4 )   722 - 731   2012.10

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    DOI: 10.1016/j.celrep.2012.08.041

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  • In vitro reconstitution of SV40 particles that are composed of VP1/2/3 capsid proteins and nucleosomal DNA and direct efficient gene transfer Reviewed

    Teruya Enomoto, Iwao Kukimoto, Masa-aki Kawano, Yuki Yamaguchi, Arnold J. Berk, Hiroshi Handa

    VIROLOGY   420 ( 1 )   1 - 9   2011.11

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    DOI: 10.1016/j.virol.2011.08.014

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  • Global analysis for functional residues of histone variant Htz1 using the comprehensive point mutant library Reviewed

    Ayumi Kawano, Yohei Hayashi, Shuhei Noguchi, Hiroshi Handa, Masami Horikoshi, Yuki Yamaguchi

    GENES TO CELLS   16 ( 5 )   590 - 607   2011.5

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    DOI: 10.1111/j.1365-2443.2011.01512.x

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  • Erythropoiesis is regulated by the transcription elongation factor Foggy/Spt5 through gata1 gene regulation Reviewed

    Takuya Taneda, Wenyan Zhu, Qingfu Cao, Hajime Watanabe, Yuki Yamaguchi, Hiroshi Handa, Tadashi Wada

    GENES TO CELLS   16 ( 2 )   231 - 242   2011.2

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    DOI: 10.1111/j.1365-2443.2010.01481.x

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  • Promoter-proximal pausing and its release: Molecular mechanisms and physiological functions Reviewed

    Kunitoshi Chiba, Junichi Yamamoto, Yuki Yamaguchi, Hiroshi Handa

    EXPERIMENTAL CELL RESEARCH   316 ( 17 )   2723 - 2730   2010.10

  • Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation Reviewed

    Sol Kim, Junichi Yamamoto, Yexi Chen, Masatoshi Aida, Tadashi Wada, Hiroshi Handa, Yuki Yamaguchi

    GENES TO CELLS   15 ( 9 )   1003 - 1013   2010.9

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    DOI: 10.1111/j.1365-2443.2010.01436.x

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  • Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the leucine-mTOR signaling pathway Reviewed

    Kanako Kume, Yosuke Iizumi, Masashi Shimada, Yuki Ito, Tsutomu Kishi, Yuki Yamaguchi, Hiroshi Handa

    GENES TO CELLS   15 ( 4 )   339 - 349   2010.4

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    DOI: 10.1111/j.1365-2443.2010.01385.x

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  • [New development in research of transcription elongation].

    Yuki Yamaguchi

    Seikagaku. The Journal of Japanese Biochemical Society   2010.3

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  • Identification of a Primary Target of Thalidomide Teratogenicity Reviewed

    Takumi Ito, Hideki Ando, Takayuki Suzuki, Toshihiko Ogura, Kentaro Hotta, Yoshimasa Imamura, Yuki Yamaguchi, Hiroshi Handa

    SCIENCE   327 ( 5971 )   1345 - 1350   2010.3

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    DOI: 10.1126/science.1177319

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  • Identification of Dynamin-2-Mediated Endocytosis as a New Target of Osteoporosis Drugs, Bisphosphonates

    Yuka Masaike, Takeshi Takagi, Masataka Hirota, Joe Yamada, Satoru Ishihara, Tetsu M. C. Yung, Takamasa Inoue, Chika Sawa, Hiroshi Sagara, Satoshi Sakamoto, Yasuaki Kabe, Yasuyuki Takahashi, Yuki Yamaguchi, Hiroshi Handa

    MOLECULAR PHARMACOLOGY   77 ( 2 )   262 - 269   2010.2

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    DOI: 10.1124/mol.109.059006

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  • Identification of Dynamin-2-Mediated Endocytosis as a New Target of Osteoporosis Drugs, Bisphosphonates Reviewed

    Yuka Masaike, Takeshi Takagi, Masataka Hirota, Joe Yamada, Satoru Ishihara, Tetsu M. C. Yung, Takamasa Inoue, Chika Sawa, Hiroshi Sagara, Satoshi Sakamoto, Yasuaki Kabe, Yasuyuki Takahashi, Yuki Yamaguchi, Hiroshi Handa

    Molecular Pharmacology   77 ( 2 )   262 - 269   2010.2

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  • DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA polymerase II elongation

    Yexi Chen, Yuki Yamaguchi, Yuta Tsugeno, Junichi Yamamoto, Tomoko Yamada, Mitsuhiro Nakamura, Koji Hisatake, Hiroshi Handa

    GENES & DEVELOPMENT   23 ( 23 )   2765 - 2777   2009.12

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  • Repression of RNA Polymerase II Elongation In Vivo Is Critically Dependent on the C-Terminus of Spt5

    Hui Chen, Xavier Contreras, Yuki Yamaguchi, Hiroshi Handa, B. Matija Peterlin, Su Guo

    PLOS ONE   4 ( 9 )   e6918   2009.9

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    DOI: 10.1371/journal.pone.0006918

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  • Cellular dynamics of the negative transcription elongation factor NELF

    Tetsu M. C. Yung, Takashi Narita, Toshiharu Komori, Yuki Yamaguchi, Hiroshi Handa

    EXPERIMENTAL CELL RESEARCH   315 ( 10 )   1693 - 1705   2009.6

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    DOI: 10.1016/j.yexcr.2009.02.013

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  • Incorporation of 8-hydroxyguanosine (8-oxo-7,8-dihydroguanosine) 5&apos;-triphosphate by bacterial and human RNA polymerases

    Hiroyuki Kamiya, Akihiro Suzuki, Yuki Yamaguchi, Hiroshi Handa, Hideyoshi Harashima

    FREE RADICAL BIOLOGY AND MEDICINE   46 ( 12 )   1703 - 1707   2009.6

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    DOI: 10.1016/j.freeradbiomed.2009.04.005

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  • Mono-(2-ethylhexyl) phthalate Targets Glycogen Debranching Enzyme and Affects Glycogen Metabolism in Rat Testis

    Chikanori Kuramori, Yasuyoshi Hase, Koichi Hoshikawa, Keiko Watanabe, Takeyuki Nishi, Takako Hishiki, Tomoyoshi Soga, Akihiro Nashimoto, Yasuaki Kabe, Yuki Yamaguchi, Hajime Watanabe, Kohsuke Kataoka, Makoto Suematsu, Hiroshi Handa

    TOXICOLOGICAL SCIENCES   109 ( 1 )   143 - 151   2009.5

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    DOI: 10.1093/toxsci/kfp041

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  • Role of human transcription elongation factor DSIF in the suppression of senescence and apoptosis

    Toshiharu Komori, Naoto Inukai, Tomoko Yamada, Yuki Yamaguchi, Hiroshi Handa

    GENES TO CELLS   14 ( 3 )   343 - 354   2009.3

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    DOI: 10.1111/j.1365-2443.2008.01273.x

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  • Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus

    Chikanori Kuramori, Motoki Azuma, Kanako Kume, Yuki Kaneko, Atsushi Inoue, Yuki Yamaguchi, Yasuaki Kabe, Takamitsu Hosoya, Masahiro Kizaki, Makoto Suematsu, Hiroshi Handa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   379 ( 2 )   519 - 525   2009.2

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    DOI: 10.1016/j.bbrc.2008.12.103

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  • Development and Application of High-Performance Affinity Beads: Toward Chemical Biology and Drug Discovery

    Satoshi Sakamoto, Yasuaki Kabe, Mamoru Hatakeyama, Yuki Yamaguchi, Hiroshi Handa

    CHEMICAL RECORD   9 ( 1 )   66 - 85   2009

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    DOI: 10.1002/tcr.20170

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  • 転写制御とエピジェネティクス—ゲノムデコードに向けて

    山口雄輝, 半田宏

    2008.12

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  • Adenine Nucleotide Translocator Transports Haem Precursors into Mitochondria

    Motoki Azuma, Yasuaki Kabe, Chikanori Kuramori, Masao Kondo, Yuki Yamaguchi, Hiroshi Handa

    PLOS ONE   3 ( 8 )   e3070   2008.8

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    DOI: 10.1371/journal.pone.0003070

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  • A new APE1/Ref-1-dependent pathway leading to reduction of NF-kappa B and AP-1, and activation of their DNA-binding activity

    Kozue Ando, Satoshi Hirao, Yasuaki Kabe, Yuji Ogura, Iwao Sato, Yuki Yamaguchi, Tadashi Wada, Hiroshi Handa

    NUCLEIC ACIDS RESEARCH   36 ( 13 )   4327 - 4336   2008.8

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    DOI: 10.1093/nar/gkn416

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  • Presentation of functional foreign peptides on the surface of SV40 virus-like particles

    Ryou-u Takahashi, Shin-nosuke Kanesashi, Takamasa Inoue, Teruya Enomoto, Masa-aki Kawano, Hiroko Tsukamoto, Fumitaka Takeshita, Takeshi Imai, Takahiro Ochiya, Kohsuke Kataoka, Yuki Yamaguchi, Hiroshi Handa

    JOURNAL OF BIOTECHNOLOGY   135 ( 4 )   385 - 392   2008.7

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    DOI: 10.1016/j.jbiotec.2008.05.012

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  • Development of a chemical screening system using aqueorin-fused protein

    Masafumi Suzuki, Shoichiro Furukawa, Chikanori Kuramori, Chika Sawa, Yasuaki Kabe, Mitsuhiro Nakamura, Jun-ichi Sawada, Yuki Yamaguchi, Satoshi Sakamoto, Satoshi Inouye, Hiroshi Handa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   368 ( 3 )   600 - 605   2008.4

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    DOI: 10.1016/j.bbrc.2008.01.107

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  • Atirazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm Reviewed

    Yasuyoshi Hase, Michiko Tatsuno, Takeyuki Nishi, Kosuke Kataoka, Yasuaki Kabe, Yuki Yamaguchi, Nobuaki Ozawa, Michiya Natori, Hiroshi Handa, Hajime Watanabe

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   366 ( 1 )   66 - 72   2008.2

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    DOI: 10.1016/j.bbrc.2007.11.107

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  • Evidence that SV40VP1-DNA interactions contribute to the assembly of 40-nm spherical viral particles Reviewed

    Hiroko Tsukamoto, Masa-aki Kawano, Takamasa Inoue, Teruya Enomoto, Ryou-u Takahashi, Naoki Yokoyama, Noriaki Yamamoto, Takeshi Imai, Kohsuke Kataoka, Yuki Yamaguchi, Hiroshi Handa

    GENES TO CELLS   12 ( 11 )   1267 - 1279   2007.11

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    DOI: 10.1111/j.1365-2443.2007.01134.x

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  • Hepatitis delta antigen binds to the clamp of RNA polymerase II and affects transcriptional fidelity Reviewed

    Yuki Yamaguchi, Takashi Mura, Sittinan Chanarat, Sachiko Okamoto, Hiroshi Handa

    GENES TO CELLS   12 ( 7 )   863 - 875   2007.7

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    DOI: 10.1111/j.1365-2443.2007.01094.x

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  • Differential regulation of NF-kappa B by elongation factors is determined by core promoter type Reviewed

    Liat Amir-Zilberstein, Elena Ainbinder, Leanne Toube, Yuki Yamaguchi, Hiroshi Handa, Rivka Dikstein

    MOLECULAR AND CELLULAR BIOLOGY   27 ( 14 )   5246 - 5259   2007.7

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    DOI: 10.1128/MCB.00586-07

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  • DSIF contributes to transcriptional activation by DNA-binding activators by preventing pausing during transcription elongation Reviewed

    Wenyan Zhu, Tadashi Wada, Sachiko Okabe, Takuya Taneda, Yuki Yamaguchi, Hiroshi Handa

    NUCLEIC ACIDS RESEARCH   35 ( 12 )   4064 - 4075   2007.6

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    DOI: 10.1093/nar/gkm430

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  • NELF interacts with CBC and participates in 3 ' end processing of replication-dependent histone rnRNAs Reviewed

    Takashi Narita, Tetsu M. C. Yung, Junichi Yamamoto, Yasunori Tsuboi, Hideyuki Tanabe, Kiyoji Tanaka, Yuki Yamaguchi, Hiroshi Handa

    MOLECULAR CELL   26 ( 3 )   349 - 365   2007.5

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    DOI: 10.1016/j.molcel.2007.04.011

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  • Identification of a chemical substructure that is immobilized to ferrite nanoparticles (FP)

    Kosuke Nishio, Nobuyuki Gokon, Makoto Hasegawa, Yuji Ogura, Morihito Ikeda, Hiroki Narimatsu, Masaru Tada, Yuki Yamaguchi, Satoshi Sakamoto, Masanori Abe, Hiroshi Handa

    COLLOIDS AND SURFACES B-BIOINTERFACES   54 ( 2 )   249 - 253   2007.2

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    DOI: 10.1016/j.colsurfb.2006.10.039

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  • Adeno-associated virus site-specific integration is regulated by TRP-185(del)

    Noriaki Yamamoto, Masato Suzuki, Masa-aki Kawano, Takamasa Inoue, Ryou-u Takahashi, Hiroko Tsukamoto, Teruya Enomoto, Yuki Yamaguchi, Tadashi Wada, Hiroshi Handa

    JOURNAL OF VIROLOGY   81 ( 4 )   1990 - 2001   2007.2

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    DOI: 10.1128/JVI.02014-06

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  • hnRNP-U enhances the expression of specific genes by stabilizing mRNA

    Masato Yugami, Yasuaki Kabe, Yuki Yamaguchi, Tadashi Wada, Hiroshi Handa

    FEBS LETTERS   581 ( 1 )   1 - 7   2007.1

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    DOI: 10.1016/j.febslet.2006.11.062

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  • Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3 '-UTRs

    Tomohiro Kubo, Tadashi Wada, Yuki Yamaguchi, Akira Shimizu, Hiroshi Handa

    NUCLEIC ACIDS RESEARCH   34 ( 21 )   6264 - 6271   2006.12

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    DOI: 10.1093/nar/gkl794

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  • A new mechanism of methotrexate action revealed by target screening with affinity beads

    Hitoshi Uga, Chikanori Kuramori, Akiko Ohta, Yasunori Tsuboi, Hiroshi Tanaka, Mamoru Hatakeyama, Yuki Yamaguchi, Takashi Takahashi, Masahiro Kizaki, Hiroshi Handa

    MOLECULAR PHARMACOLOGY   70 ( 5 )   1832 - 1839   2006.11

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    DOI: 10.1124/mol.106.025866

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  • Transcriptional pausing caused by NELF plays a dual role in regulating immediate-early expression of the junB gene

    Masatoshi Aida, Yexi Chen, Koichi Nakajima, Yuki Yamaguchi, Tadashi Wada, Hiroshi Handa

    MOLECULAR AND CELLULAR BIOLOGY   26 ( 16 )   6094 - 6104   2006.8

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    DOI: 10.1128/MCB.02366-05

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  • TFII-I down-regulates a subset of estrogen-responsive genes through its interaction with an initiator element and estrogen receptor alpha

    Y Ogura, M Azuma, Y Tsuboi, Y Kabe, Y Yamaguchi, T Wada, H Watanabe, H Handa

    GENES TO CELLS   11 ( 4 )   373 - 381   2006.4

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    DOI: 10.1111/j.1365-2443.2006.00952.x

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  • P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation Reviewed

    T Yamada, Y Yamaguchi, N Inukai, S Okamoto, T Mura, H Handa

    MOLECULAR CELL   21 ( 2 )   227 - 237   2006.1

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    DOI: 10.1016/j.molcel.2005.11.024

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  • Hepatitis Delta Virus

    H, a, Y., Yamaguchi, Y.

    Vol.   2006

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  • ケミカルバイオロジー・ケミカルゲノミクス

    山口雄輝

    Vol.   2005.11

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  • 転写研究集中マスター

    山口雄輝

    2005.9

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  • GABP, HCF-1 and YY1 are involved in Rb gene expression during myogenesis

    S Delehouzee, T Yoshikawa, C Sawa, J Sawada, T Ito, M Omori, T Wada, Y Yamaguchi, Y Kabe, H Handa

    GENES TO CELLS   10 ( 7 )   717 - 731   2005.7

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    DOI: 10.1111/j.1365-2443.2005.00873.x

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  • Transdifferentiation of the retinal pigment epithelia to the neural retina by transfer of the Pax6 transcriptional factor

    N Azuma, K Tadokoro, A Asaka, M Yamada, Y Yamaguchi, H Handa, S Matsushima, T Watanabe, Y Kida, T Ogura, M Torii, K Shimamura, M Nakafuku

    HUMAN MOLECULAR GENETICS   14 ( 8 )   1059 - 1068   2005.4

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    DOI: 10.1093/hmg/ddi098

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  • 科学英語論文の赤ペン添削講座

    山口雄輝

    2005.3

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  • Selective ligand purification using high-performance affinity beads

    Y Ohtsu, R Ohba, Y Imamura, M Kobayashi, H Hatori, T Zenkoh, M Hatakeyama, T Manabe, M Hino, Y Yamaguchi, K Kataoka, H Kawaguchi, H Watanabe, H Handa

    ANALYTICAL BIOCHEMISTRY   338 ( 2 )   245 - 252   2005.3

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    DOI: 10.1016/j.ab.2004.10.006

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  • Mediator requirement for both recruitment and postrecruitment steps in transcription initiation

    G Wang, MA Balamotis, JL Stevens, Y Yamaguchi, H Handa, AJ Berk

    MOLECULAR CELL   17 ( 5 )   683 - 694   2005.3

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    DOI: 10.1016/j.molcel.2005.02.010

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  • The Pax6 isoform bearing an alternative spliced exon promotes the development of the neural retinal structure

    N Azuma, K Tadokoro, A Asaka, M Yamada, Y Yamaguchi, H Handa, S Matsushima, T Watanabe, S Kohsaka, Y Kida, T Shiraishi, T Ogura, K Shimamura, M Nakafuku

    HUMAN MOLECULAR GENETICS   14 ( 6 )   735 - 745   2005.3

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    DOI: 10.1093/hmg/ddi069

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  • NF-Y is essential for the recruitment of RNA polymerase II and inducible transcription of several CCAAT box-containing genes

    Y Kabe, J Yamada, H Uga, Y Yamaguchi, T Wada, H Handa

    MOLECULAR AND CELLULAR BIOLOGY   25 ( 1 )   512 - 522   2005.1

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    DOI: 10.1128/MCB.25.1.512-522.2005

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  • Molecular characterization of Drosophila NELF

    CH Wu, C Lee, RP Fan, MJ Smith, Y Yamaguchi, H Handa, DS Gilmour

    NUCLEIC ACIDS RESEARCH   33 ( 4 )   1269 - 1279   2005

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    DOI: 10.1093/nar/gki274

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  • Attenuation of estrogen receptor alpha-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor

    SE Aiyar, JL Sun, AL Blair, CA Moskaluk, YZ Lu, QN Ye, Y Yamaguchi, A Mukherjee, DM Ren, H Handa, R Li

    GENES & DEVELOPMENT   18 ( 17 )   2134 - 2146   2004.9

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    DOI: 10.1101/gad.1214104

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  • Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila

    BH Jennings, S Shah, Y Yamaguchi, M Seki, RG Phillips, H Handa, D Ish-Horowicz

    CURRENT BIOLOGY   14 ( 18 )   1680 - 1684   2004.9

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    DOI: 10.1016/j.cub.2004.08.066

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  • [Analyses of biomacromolecules by electrophoresis].

    Yuki Yamaguchi

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   2004.8

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  • Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells

    S Oshima, T Nakamura, S Namiki, E Okada, K Tsuchiya, R Okamoto, M Yamazaki, T Yokota, M Aida, Y Yamaguchi, T Kanai, H Handa, M Watanabe

    MOLECULAR AND CELLULAR BIOLOGY   24 ( 14 )   6298 - 6310   2004.7

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    DOI: 10.1128/MCB.24.14.6298-6310.2004

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  • Human Spt6 stimulates transcription elongation by RNA polymerase II in vitro

    M Endoh, WY Zhu, J Hasegawa, H Watanabe, DK Kim, M Aida, N Inukai, T Narita, T Yamada, A Furuya, H Sato, Y Yamaguchi, SS Mandal, D Remberg, T Wada, H Handa

    MOLECULAR AND CELLULAR BIOLOGY   24 ( 8 )   3324 - 3336   2004.4

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    DOI: 10.1128/MCB.24.8.3324-3336.2004

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  • Elongation inhibition by DRB sensitivity-inducing factor is regulated by the A20 promoter via a novel negative element and NF-kappa B

    E Ainbinder, L Amir-Zilberstein, Y Yamaguchi, H Handa, R Dikstein

    MOLECULAR AND CELLULAR BIOLOGY   24 ( 6 )   2444 - 2454   2004.3

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    DOI: 10.1128/MCB.24.6.2444-2454.2004

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  • A novel hydrogen peroxide-induced phosphorylation and ubiquitination pathway leading to RNA polymerase II proteolysis

    N Inukai, Y Yamaguchi, Kuraoka, I, T Yamada, S Kamijo, J Kato, K Tanaka, H Handa

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 9 )   8190 - 8195   2004.2

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    DOI: 10.1074/jbc.M311412200

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  • キーワードで理解する転写イラストマップ

    山口雄輝

    2004

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  • Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations

    N Azuma, Y Yamaguchi, H Handa, K Tadokoro, A Asaka, E Kawase, M Yamada

    AMERICAN JOURNAL OF HUMAN GENETICS   72 ( 6 )   1565 - 1570   2003.6

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    DOI: 10.1086/375555

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  • NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila

    CH Wu, Y Yamaguchi, LR Benjamin, M Horvat-Gordon, J Washinsky, E Enerly, J Larsson, A Lambertsson, H Handa, D Gilmour

    GENES & DEVELOPMENT   17 ( 11 )   1402 - 1414   2003.6

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    DOI: 10.1101/gad.1091403

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  • NTP-driven translocation by human RNA polymerase II

    YA Nedialkov, XQ Gong, SL Hovde, Y Yamaguchi, H Handa, JH Geiger, HG Yan, ZF Burton

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 20 )   18303 - 18312   2003.5

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    DOI: 10.1074/jbc.M301103200

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  • Structure-function analysis of human Spt4: evidence that hSpt4 and hSpt5 exert their roles in transcriptional elongation as parts of the DSIF complex

    D Kim, N Inukai, T Yamada, A Furuya, H Sato, Y Yamaguchi, T Wada, H Handa

    GENES TO CELLS   8 ( 4 )   371 - 378   2003.4

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    DOI: 10.1046/j.1365-2443.2003.00638.x

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  • Mechanism of H-8 inhibition of Cyclin-dependent kinase 9: study using inhibitor-immobilized matrices

    D Shima, M Yugami, M Tatsuno, T Wada, Y Yamaguchi, H Handa

    GENES TO CELLS   8 ( 3 )   215 - 223   2003.3

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    DOI: 10.1046/j.1365-2443.2003.00627.x

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  • Human transcription elongation factor NELF: Identification of novel subunits and reconstitution of the functionally active complex

    T Narita, Y Yamaguchi, K Yano, S Sugimoto, S Chanarat, T Wada, DK Kim, J Hasegawa, M Omori, N Inukai, M Endoh, T Yamada, H Handa

    MOLECULAR AND CELLULAR BIOLOGY   23 ( 6 )   1863 - 1873   2003.3

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    DOI: 10.1128/MCB.23.6.1863-1873.2003

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  • Effects of endogenous DNA base lesions on transcription elongation by mammalian RNA polymerase II - Implications for transcription-coupled DNA repair and transcriptional mutagenesis

    Kuraoka, I, M Endou, Y Yamaguchi, T Wada, H Handa, K Tanaka

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 9 )   7294 - 7299   2003.2

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    DOI: 10.1074/jbc.M208102200

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  • [Molecular switch for mRNA synthesis rate].

    Yuki Yamaguchi

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   2003.1

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  • A rapid purification method for human RNA polymerase II by two-step affinity chromatography

    J Hasegawa, M Endou, T Narita, T Yamada, Y Yamaguchi, T Wada, H Handa

    JOURNAL OF BIOCHEMISTRY   133 ( 1 )   133 - 138   2003.1

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    DOI: 10.1093/jb/mvg013

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  • Assay of transient state kinetics of elongation by human RNA polymerase II

    Nedialkov, Y.A., Gong, X.Q., Yamaguchi, Y., H, a, H., Burton, Z.F.

    Methods in Enzymol.   2003

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  • Assay of transient state kinetics of RNA polymerase II elongation

    YA Nedialkov, XQ Gong, Y Yamaguchi, H Handa, ZF Burton

    RNA POLYMERASES AND ASSOCIATED FACTORS, PT D   371   252 - 264   2003

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  • Spatial redox regulation of a critical cysteine residue of NF-kappa B in vivo

    T Nishi, N Shimizu, M Hiramoto, L Sato, Y Yamaguchi, M Hasegawa, S Aizawa, H Tanaka, K Kataoka, H Watanabe, H Handa

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 46 )   44548 - 44556   2002.11

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    DOI: 10.1074/jbc.M202970200

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  • HIV and hepatitis delta virus: evolution takes different paths to relieve blocks in transcriptional elongation

    Y Yamaguchi, S Delehouzee, H Handa

    MICROBES AND INFECTION   4 ( 11 )   1169 - 1175   2002.9

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  • Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA

    Y Yamaguchi, N Inukai, T Narita, T Wada, H Handa

    MOLECULAR AND CELLULAR BIOLOGY   22 ( 9 )   2918 - 2927   2002.5

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    DOI: 10.1128/MCB.22.9.2918-2927.2002

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  • わかる実験医学シリーズ 転写がわかる

    山口雄輝

    2002

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  • A highly purified RNA polymerase II elongation control system

    DB Renner, Y Yamaguchi, T Wada, H Handa, DH Price

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 45 )   42601 - 42609   2001.11

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    DOI: 10.1074/jbc.M104967200

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  • Stimulation of RNA polymerase II elongation by hepatitis delta antigen

    Y Yamaguchi, J Filipovska, K Yano, A Furuya, N Inukai, T Narita, T Wada, S Sugimoto, MM Konarska, H Handa

    SCIENCE   293 ( 5527 )   124 - 127   2001.7

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    DOI: 10.1126/science.1057925

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  • Cloning of the hamster androgen receptor gene

    K Shiba, T Hamaguchi, K Kataoka, Y Yamaguchi, H Handa, K Adachi

    JOURNAL OF DERMATOLOGICAL SCIENCE   26 ( 3 )   163 - 168   2001.7

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    DOI: 10.1016/S0923-1811(00)00172-9

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  • The regulation of elongation by eukaryotic RNA polymerase II: A recent view

    D Kim, Y Yamaguchi, T Wada, H Handa

    MOLECULES AND CELLS   11 ( 3 )   267 - 274   2001.6

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  • SPT genes: Key players in the regulation of transcription, chromatin structure and other cellular processes

    Y Yamaguchi, T Narita, N Inukai, T Wada, H Handa

    JOURNAL OF BIOCHEMISTRY   129 ( 2 )   185 - 191   2001.2

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  • The regulation of elongation by eukaryotic RNA polymerase II: A recent view.

    Kim, D., Yamaguchi Y., Wada, T., H, a, H.

    Mol. Cells   2001

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  • A regulator of transcriptional elongation controls vertebrate neuronal development

    S Guo, Y Yamaguchi, S Schilbach, T Wada, J Lee, A Goddard, D French, H Handa, A Rosenthal

    NATURE   408 ( 6810 )   366 - 369   2000.11

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    DOI: 10.1038/35042590

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  • [Mechanism of basal transcription]

    Yuki Yamaguchi

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   2000.6

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  • [Regulatory mechanism of transcription elongation: DRB-sensitive elongation control machinery]

    Yuki Yamaguchi

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   2000.6

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  • FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH

    T Wada, G Orphanides, J Hasegawa, DK Kim, D Shima, Y Yamaguchi, A Fukuda, K Hisatake, S Oh, D Reinberg, H Handa

    MOLECULAR CELL   5 ( 6 )   1067 - 1072   2000.6

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    DOI: 10.1016/S1097-2765(00)80272-5

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  • ゲノムからの情報発現 転写因子とその機能

    山口雄輝

    2000

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  • BioScience用語ライブラリー新版

    山口雄輝

    1999.9

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  • Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies

    N Azuma, Y Yamaguchi, H Handa, M Hayakawa, A Kanai, M Yamada

    AMERICAN JOURNAL OF HUMAN GENETICS   65 ( 3 )   656 - 663   1999.9

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    DOI: 10.1086/302529

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  • Tat-SF1 protein associates with RAP30 and human SPT5 proteins

    JB Kim, Y Yamaguchi, T Wada, H Handa, PA Sharp

    MOLECULAR AND CELLULAR BIOLOGY   19 ( 9 )   5960 - 5968   1999.9

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  • PAX6 expression in the developing human eye

    S Nishina, S Kohsaka, Y Yamaguchi, H Handa, A Kawakami, H Fujisawa, N Azuma

    BRITISH JOURNAL OF OPHTHALMOLOGY   83 ( 6 )   723 - 727   1999.6

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  • NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation

    Y Yamaguchi, T Takagi, T Wada, K Yano, A Furuya, S Sugimoto, J Hasegawa, H Handa

    CELL   97 ( 1 )   41 - 51   1999.4

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    DOI: 10.1016/S0092-8674(00)80713-8

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  • Structure and function of the human transcription elongation factor DSIF

    Y Yamaguchi, T Wada, D Watanabe, T Takagi, J Hasegawa, H Handa

    JOURNAL OF BIOLOGICAL CHEMISTRY   274 ( 12 )   8085 - 8092   1999.3

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    DOI: 10.1074/jbc.274.12.8085

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  • 転写伸長反応を抑制する因子群の同定と解析

    山口雄輝

    1999.2

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  • Purification of DNA binding proteins. in High resolution chromatography: A practical approach

    H, a, H., Yamaguchi, Y., Wada, T.

    1999

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  • Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription invitro

    T. Wada

    The EMBO Journal   17 ( 24 )   7395 - 7403   1998.12

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    DOI: 10.1093/emboj/17.24.7395

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  • Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro

    T Wada, T Takagi, Y Yamaguchi, D Watanabe, H Handa

    EMBO JOURNAL   17 ( 24 )   7395 - 7403   1998.12

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    DOI: 10.1093/emboj/17.24.7395

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  • Casein kinase II interacts with the bZIP domains of several transcription factors

    Y Yamaguchi, T Wada, F Suzuki, T Takagi, J Hasegawa, H Handa

    NUCLEIC ACIDS RESEARCH   26 ( 16 )   3854 - 3861   1998.8

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    DOI: 10.1093/nar/26.16.3854

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  • DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs

    T Wada, T Takagi, Y Yamaguchi, A Ferdous, T Imai, S Hirose, S Sugimoto, K Yano, GA Hartzog, F Winston, S Buratowski, H Handa

    GENES & DEVELOPMENT   12 ( 3 )   343 - 356   1998.2

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    DOI: 10.1101/gad.12.3.343

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  • Interplay between positive and negative elongation factors: drawing a new view of DRB

    Y Yamaguchi, T Wada, H Handa

    GENES TO CELLS   3 ( 1 )   9 - 15   1998.1

  • Autoregulation of Pax6 transcriptional activation by two distinct DNA-binding subdomains of the paired domain

    Y Yamaguchi, J Sawada, M Yamada, H Handa, N Azuma

    GENES TO CELLS   2 ( 4 )   255 - 261   1997.4

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    DOI: 10.1046/j.1365-2443.1997.1170315.x

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  • Copurification of casein kinase II with transcription factor ATF/E4TF3

    T Wada, T Takagi, Y Yamaguchi, H Kawase, M Hiramoto, A Ferdous, M Takayama, KAW Lee, HC Hurst, H Handa

    NUCLEIC ACIDS RESEARCH   24 ( 5 )   876 - 884   1996.3

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    DOI: 10.1093/nar/24.5.876

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  • BioScience用語ライブラリー

    山口雄輝

    1995.9

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▼display all

Books

  • History of IMiDs and Protein Degradation as a Pharmacological Modality

    ( Original_author: Junichi Yamamoto, Tomoko Asatsuma-Okumura, Takumi Ito, Yuki Yamaguchi, Hiroshi Handa ,  Chapter 8)

    John Wiley & Sons  2022.11  ( ISBN:9781119774129

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    Responsible for pages:283–315   Language:English   Book type:Scholarly book

    DOI: 10.1002/9781119774198

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  • 遺伝子発現制御機構 クロマチン,転写制御,エピジェネティクス

    山口 雄輝( Role: Contributor)

    東京化学同人  2017.4 

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  • テツヤ、国際学会いってらっしゃい : 発表・懇親会・ラボツアー編

    Ko, Kyota, Gillett, Simon, 近藤, 科江, 山口, 雄輝

    羊土社  2014.12  ( ISBN:9784758108454

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    Total pages:198, 1p  

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  • テツヤ、ディスカッションしようか : スピーチ・議論・座長編

    Ko, Kyota, Gillett, Simon, 近藤, 科江, 山口, 雄輝

    羊土社  2014.12  ( ISBN:9784758108461

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    Total pages:205, 1p  

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  • 基礎からしっかり学ぶ生化学

    山口, 雄輝, 成田, 央

    羊土社  2014.11  ( ISBN:9784758120500

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    Total pages:244p   Language:Japanese  

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  • 新しい遺伝子工学 新版

    山口雄輝( Role: Contributor)

    朝倉書店  2014.9 

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  • 転写制御とエピジェネティクス—ゲノムデコードに向けて—

    山口 雄輝( Role: Contributor)

    南山堂  2008.12 

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  • 新しい遺伝子工学

    山口 雄輝( Role: Contributor)

    昭晃堂  2006.7 

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  • Hepatitis Delta Virus

    Handa, Y, Yamaguchi, Y

    Landes Bioscience / Springer Science+Business Media  2006 

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  • ケミカルバイオロジー・ケミカルゲノミクス

    山口 雄輝

    シュプリンガー・フェアラーク  2005.11 

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  • 転写研究集中マスター

    半田 宏, 和田 忠士, 山口 雄輝( Role: Edit)

    羊土社  2005.9 

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  • 科学英語論文の赤ペン添削講座

    山口 雄輝( Role: Sole author)

    羊土社  2005.3 

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  • キーワードで理解する転写イラストマップ

    山口 雄輝

    羊土社  2004 

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  • わかる実験医学シリーズ 転写がわかる

    山口 雄輝

    羊土社  2002 

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  • ゲノムからの情報発現 転写因子とその機能

    山口 雄輝

    シュプリンガー・フェアラーク  2000 

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  • BioScience用語ライブラリー新版

    山口 雄輝( Role: Contributor)

    羊土社  1999.9 

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  • Purification of DNA binding proteins. in High resolution chromatography: A practical approach

    Oxford University Press  1999 

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MISC

  • The multi-omics analysis of the components of nuclear bodies using antibody-based in situ biotinylation technique.

    野口慶介, 鈴木秀文, 阿部竜太, 堀内恵子, 秋山智彦, 池陽子, 井野洋子, 木村弥生, 梁明秀, 梁明秀, 山口雄輝, 高橋秀尚

    日本電気泳動学会シンポジウム講演要旨集   73rd (CD-ROM)   2023

  • Identification of CRL4CRBN neosubstrates involved in thalidomide teratogenicity

    朝妻知子, 伊藤拓水, 山口雄輝, 半田宏

    日本農芸化学会大会講演要旨集(Web)   2021   2021

  • 新規のビオチン標識手法による核内構造体カハールボディ構成因子の網羅的解析

    野口慶介, 鈴木秀文, 阿部竜太, 池陽子, 井野洋子, 木村弥生, 梁明秀, 山口雄輝, 高橋秀尚

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

  • 転写反応の生化学

    山口 雄輝

    生体の科学   vol. 68   2017.6

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    DOI: 10.11477/mf.2425200618

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  • DNA損傷応答における転写抑制メカニズムとその生理的意義の解析

    鈴木秀文, 前田亮, 木村宏, 浦聖恵, 田村隆明, 山口雄輝

    日本生化学会大会(Web)   90th   2017

  • メディエーター複合体による転写終結制御機構

    高橋秀尚, 柴田美音, 瀧川一学, 渡部昌, 築山忠維, 山本淳一, 山口雄輝, 藤井聡, 飯田緑, RANJAN Amol, SATO Shigeo, TOMOMORI‐SATO Chieri, CONAWAY Joan, CONAWAY Ronald, 畠山鎮次

    日本生化学会大会(Web)   90th   ROMBUNNO.4P2T15‐06(3P‐0635) (WEB ONLY) - 0635)]   2017

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    J-GLOBAL

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  • 抗炎症薬サリチル酸が示す生体内作用メカニズムの解析

    坂本聡, VIPUL Gupta, LIU Shujie, 安藤秀樹, 舘野峻平, 金子裕生, 湯上真人, 石井亮平, 濡木理, 山口雄輝, 半田宏

    日本化学会春季年会講演予稿集(CD-ROM)   97th   2017

  • エトポシドによるDNA傷害応答においてTLPは転写を不活性化することで細胞死を誘導する

    鈴木秀文, 前田亮, 木村宏, 浦聖恵, 山口雄輝, 田村隆明

    日本分子生物学会年会プログラム・要旨集(Web)   39th   2016

  • E3ユビキチンリガーゼの基質認識レセプターCRBNとポマリドマイド依存的な基質Aiolosの生化学的解析

    片山美樹, 伊藤拓水, 安藤秀樹, 山口雄輝, 半田宏

    日本分子生物学会年会プログラム・要旨集(Web)   37th   2014

  • サリドマイドターゲット分子CRBNの生化学的解析

    飯田結, 伊藤拓水, 安藤秀樹, 山口雄輝, 半田宏

    日本分子生物学会年会プログラム・要旨集(Web)   36th   2013

  • 多発性骨髄腫におけるCRBN結合因子の探索及び解析

    舩造正英, 伊藤拓水, 安藤秀樹, 山口雄輝, 半田宏

    日本分子生物学会年会プログラム・要旨集(Web)   36th   2013

  • ナノ磁性微粒子を用いたサリドマイド標的タンパク質の同定

    羽生尚広, 伊藤拓水, 安藤秀樹, 山口雄輝, 半田宏

    多摩川技報   29 ( 1 )   2012

  • サリドマイドによる催奇形性の分子機構

    伊藤拓水, 安藤秀樹, 山口雄輝, 半田宏, 半田宏

    日本骨代謝学会学術集会プログラム抄録集   29th   2011

  • サリチル酸の標的因子の同定と機能解析

    LIU Shujie, GUPTA Vipul, 安藤秀樹, 加部泰明, 山口雄輝, 半田宏, 半田宏

    日本分子生物学会年会プログラム・要旨集(Web)   34th   2011

  • S16-4 サリドマイドによる催奇性の分子機構 : ナノビーズ技術を用いたアプローチ(シンポジウムS16 薬物有害反応の発現機構と予測の新展開,臨床から学び臨床へと還元する医療薬学)

    伊藤 拓水, 安藤 秀樹, 山口 雄輝, 半田 宏

    日本医療薬学会年会講演要旨集   20 ( 0 )   236 - 236   2010.10

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  • 転写伸長研究の新展開

    山口 雄輝

    日本生化学会   2010.3

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  • サリドマイド催奇性の原因因子の発見

    伊藤拓水, 安藤秀樹, 鈴木孝幸, 小椋利彦, 山口雄輝, 半田宏

    実験医学   28   2115 - 2118   2010

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  • ゼブラフィッシュ発生工学を用いたサリドマイド催奇性機構の解明

    安藤秀樹, 伊藤拓水, 堀田健太郎, 山口雄輝, 半田宏, 半田宏

    生化学   2010

  • サリドマイド催奇性における主要な標的因子の同定

    伊藤拓水, 安藤秀樹, 鈴木孝幸, 小椋利彦, 山口雄輝, 半田宏, 半田宏

    生化学   2010

  • サリドマイド催奇性,標的因子の同定

    安藤秀樹, 伊藤拓水, 鈴木孝幸, 小椋利彦, 山口雄輝, 半田宏, 半田宏

    細胞工学   29 ( 8 )   2010

  • サリドマイド催奇性における標的因子の同定

    伊藤拓水, 安藤秀樹, 堀田健太郎, 山口雄輝, 半田宏, 半田宏

    生化学   2009

  • ゼブラフィッシュ初期発生における転写伸長因子P-TEFbの役割

    種田拓也, CAO Qing Fu, 安藤秀樹, 和田忠士, 山口雄輝, 半田宏, 半田宏

    日本分子生物学会年会講演要旨集   32nd ( Vol.1 )   2009

  • ヌクレオチド除去修復に関わる構造特異的エンドヌクレアーゼXPGの機能解析

    成田央, 伊藤伸介, 谷本雅史, 山口雄輝, 半田宏, 田中亀代次

    生化学   2008

  • Mechanisms of cell cycle-dependent histone expression

    Protein, nucleic acid and enzyme   52 ( 14 )   1857 - 1862   2007.11

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  • 転写因子による生命現象解明の最前線

    山口 雄輝, 半田 宏, 和田 忠士

    実験医学増刊   25   2007.6

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  • mRNA合成速度の分子スイッチ

    和田 忠士, 山口 雄輝, 半田 宏

    蛋白質核酸酵素   48 ( 1 )   9 - 17   2003.1

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  • 正反対の機能を使い分ける新たな転写調節因子 RNA ポリメラーゼ II の転写反応を制御, 神経発達における役割にも興味

    山口 雄輝, 半田 宏

    化学と生物   39 ( 4 )   210 - 211   2001.4

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  • Infectious Disease D型肝炎ウイルス(HDV)の増殖メカニズム

    山口 雄輝, 半田 宏

    遺伝子医学   5 ( 4 )   664 - 669   2001

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    Other Link: http://search.jamas.or.jp/link/ui/2002099296

  • Molecular Cell Biology on Morphogenesis of the Fovea and Evolution of the Central Vision

    AZUMA Noriyuki, NATHANS Jeremy

    104 ( 12 )   960 - 985   2000.12

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  • 転写伸長反応の制御機構--DRB感受性の伸長制御装置 (転写因子の機能--転写制御複合体形成のダイナミクス) -- (転写開始・伸長反応の制御機構)

    山口 雄輝, 和田 忠士, 半田 宏

    蛋白質核酸酵素   45 ( 9 )   1476 - 1483   2000.6

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  • 概説--基本転写のメカニズム (転写因子の機能--転写制御複合体形成のダイナミクス) -- (転写開始・伸長反応の制御機構)

    山口 雄輝, 和田 忠士, 半田 宏

    蛋白質核酸酵素   45 ( 9 )   1473 - 1475   2000.6

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  • Characterization of DSIF that regulates transcription elongation

    TAKAGI Toshiyuki, YAMAGUHI Yuki, WADA Tadashi, HASEGAWA Jun, HANDA Hiroshi

    21   408 - 408   1998.12

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  • The regulatory network of transcription elongation factors : Analysis using a drug DRB

    YAMAGUCHI Yuki, TAKAGI Toshiyuki, WADA Tadashi, HANDA Hiroshi

    21   408 - 408   1998.12

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  • DRB依存性転写阻害機構の解析

    高木 敏行, 和田 忠士, 山口 雄輝, FERDOUS Anwarul, 半田 宏

    日本分子生物学会年会プログラム・講演要旨集   19   788 - 788   1996.8

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  • 転写反応におけるカゼインキナーゼIIの役割

    半田 宏, 山口 雄輝, 高木 敏行, FERDOUS Anwarul, 今井 剛, 広瀬 進, 和田 忠士

    日本分子生物学会年会プログラム・講演要旨集   19   68 - 68   1996.8

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Presentations

  • RNAポリメラーゼIIによるヌクレオソーム転写機構の構造解析

    鯨井智也, 江原晴彦, 加藤淳子, 伊藤友子, 大屋恵梨子, 山本京香, 平井誠也, 邉見真生, 根岸留美, 小笠原光雄, 山口雄輝, 小林武彦, 滝沢由政, 関根俊一, 胡桃坂仁志

    第42回染色体ワークショップ・第23回核ダイナミクス研究会  2025.1 

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    Event date: 2025.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:グランドメルキュール別府湾  

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  • Structural insights into nucleosomal DNA transcription by RNA polymerase II International conference

    Tomoya Kujirai, Haruhiko Ehara, Junko Kato, Kyoka Yamamoto, Seiya Hirai, Takeru Fujii, Kazumitsu Maehara, Akihito Harada, Lumi Negishi, Mitsuo Ogasawara, Mikako Shirouzu, Yuki Yamaguchi, Yasuyuki Ohkawa, Yoshimasa Takizawa, Shuni-chi Sekine, Hitoshi Kurumizaka

    Transcription and Chromatin UK  2024.9 

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    Event date: 2024.9

    Language:English   Presentation type:Poster presentation  

    Venue:Newcastle upon Tyne, UK  

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  • Structural insights into chromatin transcription International conference

    Tomoya Kujirai, Haruhiko Ehara, Junko Kato, Kyoka Yamamoto, Seiya Hirai, Takeru Fujii, Kazumitsu Maehara, Akihito Harada, Lumi Negishi, Mitsuo Ogasawara, Mikako Shirouzu, Yuki Yamaguchi, Yasuyuki Ohkawa, Yoshimasa Takizawa, Shuni-chi Sekine, Hitoshi Kurumizaka

    26th IUBMB-17th FAOBMB Congress  2024.9 

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    Event date: 2024.9

    Language:English   Presentation type:Poster presentation  

    Venue:Melbourne, Australia  

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  • Structural insights into transcription elongation on chromatin in cells International conference

    Tomoya Kujirai, Haruhiko Ehara, Junko Kato, Kyoka Yamamoto, Seiya Hirai, Takeru Fujii, Kazumitsu Maehara, Akihito Harada, Lumi Negishi, Mitsuo Ogasawara, Mikako Shirouzu, Yuki Yamaguchi, Yasuyuki Ohkawa, Yoshimasa Takizawa, Shun ichi Sekine, Hitoshi Kurumizaka

    16th EMBL Conference on Transcription and Chromatin  2024.8 

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    Event date: 2024.8

    Language:English   Presentation type:Poster presentation  

    Venue:EMBL Heidelberg, Germany  

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  • RNAポリメラーゼと基本転写/修復因子TFIIHの新たな相互作用

    奥田昌彦,諏訪哲史,鈴木秀文,山口雄輝,西村善文

    第39回染色体ワークショップ・第20回核ダイナミクス研究会 

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    Event date: 2021.12

    Language:Japanese  

    Venue:オンライン開催  

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  • ナノ磁性ビーズ精製とCRISPRライブラリースクリーニングによる薬剤標的分子の網羅的同定を目指した研究

    原口大和,坂本聡,山口雄輝

    第44回日本分子生物学会 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:パシフィコ横浜  

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  • 新規ビオチン標識法を用いたマルチオミックス解析によるCajal body形成メカニズムの解明

    野口慶介,鈴木秀文,阿部竜太,池陽子,井野洋子,木村弥生,梁明秀,土井宏,田中章景,山口雄輝,高橋秀尚

    第44回日本分子生物学会 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:パシフィコ横浜  

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  • メディエーター複合体による新規の3' Pol IIポージング制御機構の解明

    鈴木秀文,阿部竜太,嶋田美穂,廣瀬智威,廣瀬博子,野口慶介,古郡華月,池陽子,安井七海,豊田敦,鈴木穣,山本達郎,斉藤典子,Ronald Conaway,Joan Conaway,山口雄輝,高橋秀尚

    第44回日本分子生物学会 

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    Event date: 2021.12

    Language:Japanese  

    Venue:パシフィコ横浜  

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  • In situ ビオチン化によるコヒーシン近傍因子の探索

    古屋智基,山口雄輝

    第44回日本分子生物学会 

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    Language:Japanese   Presentation type:Poster presentation  

    Venue:パシフィコ横浜  

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  • ポマリドミド依存的なCRBNのネオ基質ARID2の解析

    山本淳一,山口雄輝,半田宏

    第44回日本分子生物学会 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:パシフィコ横浜  

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  • 共通サブユニットRPB6を介したヒトRNAポリメラーゼと基本転写因子TFIIHの相互作用

    諏訪哲史,奥田昌彦,鈴木秀文,西村善文,山口雄輝

    第44回日本分子生物学会 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:パシフィコ横浜  

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  • RNAポリメラーゼとTFIIHの相互作用部位の細胞機能解析

    山口雄輝

    BINDS-NMR報告会  2021.11 

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    Venue:横浜市立大学  

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  • 神経変性疾患の原因であるタンパク質凝集体を選択的に分解誘導するPROTACの開発を目指した研究

    荒川翼, 山口雄輝, 坂本聡

    第46回日本分子生物学会  2023.12 

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    Venue:神戸ポートアイランド  

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  • 二次元的スクリーニング解析を駆使した既存抗がん剤の新規作用機序の解明を目指した研究

    原口大和, 坂本聡, 山口雄輝

    第45回日本分子生物学会  2022.12 

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    Venue:幕張メッセ  

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  • 転写終結と3'末端プロセシングの経路や部位の選択機構

    山口雄輝

    転写研究会ワークショップ  2025.2 

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    Venue:東京科学大学 湯島キャンパス  

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  • CRBNの病態生理学的な機能の解明

    奥村梨佳, 山口雄輝

    第47回日本分子生物学会  2024.11 

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    Venue:福岡国際会議場  

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  • 抗体を用いたin situビオチン標識法による核内構造体構成因子のマルチオミクス解析

    野口慶介, 鈴木秀文, 阿部竜太, 堀内恵子, 小野口玲菜, 秋光信佳, 秋山智彦, 池陽子, 井野洋子, 木村弥生, 梁明秀, 豊田敦, 鈴木穣, 山口雄輝, 高橋秀尚

    第47回日本分子生物学会  2024.11 

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    Venue:福岡国際会議場  

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  • 近位依存性ビオチン化による薬剤標的タンパク質の探索法の開発

    勝尾徳斗, 坂本聡, 山口雄輝

    第47回日本分子生物学会  2024.11 

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    Venue:福岡国際会議場  

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  • A focused study of uncharacterized human genes containing putative nucleic acid-interacting motifs: toward a comprehensive understanding of the human genome

    Nutchaya Muksombat, Yuki Yamaguchi

    第46回日本分子生物学会  2023.12 

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    Venue:神戸ポートアイランド  

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  • レナリドマイド耐性多発性骨髄腫細胞の生存に重要なポマリドマイド依存性CRL4CRBNのネオ基質ARID2の解析

    山本淳一, 山口雄輝, 半田宏

    第45回日本分子生物学会  2022.12 

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    Venue:幕張メッセ  

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  • ヒトRNAポリメラーゼと基本転写/修復因子TFIIHの新たな相互作用の構造生物学的研究

    奥田昌彦, 諏訪哲史, 鈴木秀文, 山口雄輝, 西村善文

    第45回日本分子生物学会  2022.12 

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    Venue:幕張メッセ  

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  • Pol IIの一時停止および核体凝集体の制御におけるメディエーター複合体の役割

    高橋秀尚, 鈴木秀文, 阿部竜太, 嶋田美穂, 廣瀬智威, 廣瀬博子, 野口慶介, 池陽子, 安井七海, 古郡華月, 山口雄輝, 豊田敦, 鈴木穣, 山本達郎, 斉藤典子, Sato Shigeo, Tomomori-Sato Chieri, Conaway Joan, Canaway Ronald

    第45回日本分子生物学会  2022.12 

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    Venue:幕張メッセ  

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  • メディエーター複合体による新規の転写スピード調節機構の解明

    鈴木秀文, 阿部竜太, 嶋田美穂, 廣瀬智威, 廣瀬博子, 野口慶介, 池陽子, 安井七海, 古郡華月, 山口雄輝, 豊田敦, 鈴木穣, 山本達郎, 斉藤典子, Sato Shigeo, Tomomori-Sato Chieri, Conaway Ronald, Conaway Joan, 高橋秀尚

    第45回日本分子生物学会  2022.11 

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  • 新規ビオチン標識法を用いたマルチオミクス解析によるCajal body構成因子の網羅的解析とCajal body形成メカニズムの解明

    野口慶介, 鈴木秀文, 阿部竜太, 池陽子, 井野洋子, 木村弥生, 梁明秀, 土井宏, 田中章景, 山口雄輝, 高橋秀尚

    第45回日本分子生物学会  2022.11 

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    Venue:幕張メッセ  

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  • PolⅡ複合体をモデルとしたタンパク質間相互作用の実験系の評価

    新垣 貴之, 徳山 遥香, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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  • TFIIH の多機能性を司るPleckstrin homology ドメインと新規標的因子の機能構造解析

    諏訪 哲史, 鈴木 秀文, 奥田 昌彦, 西村 善文, 山口 雄輝

    第41回日本分子生物学会年会  2018.11 

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  • 抗がん作用を有するカンナビノイドの作用機序の解析

    小泉 純玲, 坂本 聡, 山口 雄輝

    日本薬学会第139年会  2019.3 

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  • Molecular mechanisms controlling pathways and sites for Pol Ⅱ transcription termination

    山口 雄輝

    第41回日本分子生物学会年会  2018.11 

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  • 「遺伝情報の維持と制御の多層的理解に向けて」

    山口 雄輝, 林 眞理

    2017.12 

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  • Mechanisms that affect post-transcriptional fate of RNA polymerase II-transcribed genes

    Fajar Muhamad, Ari Zukeran, Shumpei Tateno, Junichi Yamamoto, Hiroshi Handa, Yuki Yamaguchi

    2017年度生命科学系学会合同年次大会  2017.12 

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  • メディエーター複合体による転写終結制御機構

    高橋 秀尚, 柴田 美音, 瀧川 一学, 渡部 昌, 築山 忠維, 山本 淳一, 山口 雄輝, 藤井 聡, 飯田 緑, Amol Ranjan, Shigeo Sato, Chieri Tomomori-Sato, Joan Conaway, Ronald Conaway, 畠山 鎮次

    2017年度生命科学系学会合同年次大会  2017.12 

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  • In situでのビオチン化反応を利用したタンパク質間相互作用の解析

    水止 洋孝, 新垣 貴之, 山口 雄輝

    第41回日本分子生物学会年会  2018.11 

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  • DNA損傷応答における転写抑制メカニズムとその生理的意義の解析

    鈴木 秀文, 前田 亮, 木村 宏, 浦 聖恵, 田村 隆明, 山口 雄輝

    2017年度生命科学系学会合同年次大会  2017.12 

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  • マウスES細胞における2細胞期特異的遺伝子Zscan4の転写制御機構の解明

    鈴木 翔子, 柴田 紘孝, 山口 雄輝

    2017年度生命科学系学会合同年次大会  2017.12 

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  • snRNAプロセシング因子Integrator複合体の分子構造解析

    舘野 峻平, Thiengtrong Benjarat, 山口 雄輝

    2017年度生命科学系学会合同年次大会  2017.12 

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  • NELFを中心としたポリ(A)付加部位の選択機構の解析

    山本 淳一, Fajar Muhamad, 瑞慶覧 安里, 舘野 峻平, 半田 宏, 山口 雄輝

    2017年度生命科学系学会合同年次大会  2017.12 

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  • Molecular mechanisms for polyadenylation site selection by NELF and related factors International conference

    Shumpei Tateno, Ari Zukeran, Junichi Yamamoto, Yuki Yamaguchi

    Mechanisms of Eukaryotic Transcription 2017  2017.8 

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  • タンパク質コード遺伝子の3'末端プロセシングにおけるポリ(A)付加サイト選択の作用機序の解明

    高森 朝浩, Fajar Muhamad, 山口 雄輝

    第37回染色体ワークショップ・第18回核ダイナミクス研究会  2019.12 

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  • Comprehensive identification of proximal proteins by in situ biotinylation through a specific antibody: toward proteomic analysis of liquid droplets Invited

    2019.9 

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  • 抗てんかん薬ゾニサミド、バルプロ酸の分子ターゲット探索とプテリジン代謝への影響

    荒木 勇輝, 原 怜, 坂本 聡, 山口 雄輝, 一瀬 宏

    第33回日本プテリジン研究会  2019.11 

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  • E3ユビキチンリガーゼを標的とした創薬の新展開 Invited

    山口 雄輝

    東工大創薬ゲノムシンポジウム  2019.11 

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  • Pol IIの転写終結部位を制御する分子機構

    山口 雄輝, 瑞慶覧 安里, Muhamad Fajar, 舘野 峻平, 高森 朝浩

    第42回日本分子生物学会年会  2019.12 

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  • Biochemical analyses of CRBN, the target protein for immunomodulatory drugs (IMiDs) International conference

    Satoshi Sakamoto, Takumi Ito, Yuki Yamaguchi, Hideki Ando, Hiroshi Handa

    2015.12 

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  • Elucidation of the molecular mechanisms of action of bioactive natural products using high performance affinity beads International conference

    2015.12 

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  • 多発性骨髄腫におけるPomalidomide標的因子の網羅的探索

    舘野 峻平, 飯田 緑, 藤井 聡, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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  • 新規抗がん剤の作用機構の解明

    佐倉 絵里, 舘野 峻平, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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  • NELFを中心としたmRNAの品質管理のメカニズム

    瑞慶覧 安里, 山本 淳一, 磯部 智康, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2015  2015.8 

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  • Regulatory Mechanisms for Pol II Termination Sites and 3' Processing Pathways in Higher Eukaryotes International conference

    MECHANISM OF EUKARYOTIC TRANSCRIPTION  2015.8 

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  • PolⅡの転写伸長と運命決定制御のメカニズム

    山口 雄輝

    第2回北陸エピジェネティクス研究会  2015.11 

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  • 多発性骨髄腫に対するポマリドマイドの標的因子の網羅的探索

    舘野 峻平, 飯田 緑, 藤井 聡, 山口 雄輝

    第38回日本分子生物学会年会  2015.12 

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  • 転写伸張因子DSIFのCTRを介した転写制御機構の解析

    磯部 智康, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2015  2015.8 

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  • IMiDs標的タンパク質CRBNの生化学的解析

    坂本 聡, 伊藤 拓水, 安藤 秀樹, 山口 雄輝, 半田 宏

    日本ケミカルバイオロジー学会 第10回年会  2015.6 

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  • 転写伸長段階の制御メカニズム:新たな制御因子の探索

    山口 雄輝, 磯部 智康, 曹 青福, 山本 淳一

    新学術領域研究「転写サイクル」班会議2015  2015.8 

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  • E3ユビキチンリガーゼの基質認識レセプター CRBNとポマリドマイド依存的な基質Aiolosの生化学的解析

    片山 美樹, 伊藤 拓水, 安藤 秀樹, 山口 雄輝, 半田 宏

    第37回日本分子生物学会年会  2014.11 

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  • DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes

    Junichi Yamamoto, Hiroshi Handa, Yuki Yamaguchi

    新学術領域研究「転写サイクル」冬の若手ワークショップ2015  2015.2 

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  • 転写伸長因子DSIFのリン酸化の転写伸長反応への寄与の解析

    磯部 智康, 千葉 国俊, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2015  2015.2 

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  • アフィニティビーズを利用した生物活性物質標的タンパク質の単離・同定・評価

    坂本 聡, 山口 雄輝, 半田 宏

    日本薬学会第135年会  2015.3 

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  • DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes

    山本 淳一, 半田 宏, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2014  2014.8 

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  • 転写伸長因子DSIFおよびNELFがES細胞の多分化能維持に果たす役割

    柴田 紘孝, 半田 宏, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2014  2014.8 

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  • 新規転写伸長因子ヒトRtf1が関与する転写制御の分子機構

    曹 青福, 陳 業熹, 半田 宏, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2014  2014.8 

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  • Regulatory Mechanisms for Pol II Termination Sites and 3' Processing Pathways in Higher Eukaryotes

    Yuki Yamaguchi, Junichi Yamamoto

    新学術領域研究「転写サイクル」国際シンポジウム2014  2014.11 

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  • 抗炎症薬サリチル酸の生体内作用機構の解析

    坂本 聡, Vipul Gupta, 劉 舒捷, 安藤 秀樹, 舘野 峻平, 金子 裕生, 湯上 真人, 石井 亮平, 濡木 理, 山口 雄輝, 半田 宏

    日本ケミカルバイオロジー学会 第9回年会  2014.6 

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  • ヒトRNA ポリメラーゼII 転写産物のプロセシング経路の選択機構

    山口雄輝, 山本淳一, 半田宏

    新学術領域研究「転写サイクル」班会議2014  2014.8 

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  • 転写伸長因子DSIFにリン酸化依存的に相互作用する因子の機能解析

    磯部 智康, 千葉 国俊, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2014  2014.8 

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  • 多発性骨髄腫に対するポマリドマイドの標的因子の網羅的探索

    舘野 峻平, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2014  2014.1 

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  • ゲノム上のRNAポリメラーゼ等の動的解析を目指した予備的な検討

    中村 佳奈子, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2014  2014.1 

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  • 転写伸長因子DSIFにリン酸化依存的に相互作用する因子の機能解析

    長谷川 冴妃子, 千葉 国俊, 磯部 智康, 山口 雄輝

    2014.1 

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  • ビタミンK2が引き起こすがん細胞のアポトーシス誘導機構の解析

    坂本 聡, 唐澤 慧記, 東 基記, 笠間 健嗣, 宮澤 啓介, 山口 雄輝, 半田 宏

    日本化学会第94春季年会(2014)  2014.3 

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  • Cellecta社製プール型レンチウイルスshRNAライブラリーを用いたスクリーニングデータ解析法の検討

    飯田 緑, 舘野 峻平, 山口 雄輝, 藤井 聡

    新学術領域研究「転写サイクル」冬の若手ワークショップ2014  2014.1 

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  • 転写伸長因子DSIFおよびNELFがES細胞の多分化能維持に果たす役割

    柴田 紘孝, 半田 宏, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2014  2014.1 

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  • 転写伸長因子ヒトPaf1複合体が関与する転写制御の分子機構

    曹 青福, 陳 業熹, 半田 宏, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2014  2014.1 

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  • ゲノム上のRNA ポリメラーゼ等のカイネティクス解析を目指した予備的な検討

    中村 佳奈子, 山口 雄輝

    第36回日本分子生物学会年会  2013.12 

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  • サリドマイドターゲット分子CRBN の生化学的解析

    飯田 結, 伊藤 拓水, 安藤 秀樹, 山口 雄輝, 半田 宏

    第36回日本分子生物学会年会  2013.12 

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  • 多発性骨髄腫に対するポマリドマイドの標的因子の網羅的探索

    舘野 峻平, 山口 雄輝

    第36回日本分子生物学会年会  2013.12 

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  • 多発性骨髄腫におけるCRBN 結合因子の探索及び解析

    舩造 正英, 伊藤 拓水, 安藤 秀樹, 山口 雄輝, 半田 宏

    第36回日本分子生物学会年会  2013.12 

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  • サリドマイドによる催奇性の分子機構 : ナノビーズ技術を用いたアプローチ

    伊藤 拓水, 安藤 秀樹, 山口 雄輝, 半田 宏

    日本医療薬学会年会  2010.11 

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  • DNA損傷時に誘導される転写制御の生理的意義とTLPの役割

    鈴木 秀文, 前田 亮, 木村 宏, 浦 聖恵, 山口 雄輝, 田村 隆明

    新学術領域研究「転写サイクル」冬の若手ワークショップ2017  2017.1 

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  • 抗炎症薬サリチル酸が示す生体内作用メカニズムの解析

    坂本 聡, Gupta Vipul, 劉 舒捷, 安藤 秀樹, 舘野 峻平, 金子 裕生, 湯上 真人, 石井 亮平, 濡木 理, 山口 雄輝, 半田 宏

    日本化学会年.第97春季年会  2017.3 

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  • Transcription silencing by TLP contributes to etoposide-induced apoptosis International conference

    Hidefumi Suzuki, Ryo Maeda, Hiroshi Kimura, Kiyoe Ura, Taka-aki Tamura, Yuki Yamaguchi

    Mechanisms of Eukaryotic Transcription 2017  2017.8 

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  • RNAポリメラーゼⅡ転写産物の長さを決める3’末端プロセシングの制御メカニズムの解明

    瑞慶覧 安里, 舘野 峻平, 山本 淳一, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2017  2017.1 

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  • マウスES細胞における2細胞期特異的な遺伝子の発現制御メカニズムの解析

    鈴木 翔子, 柴田 紘孝, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2017  2017.1 

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  • E3ユビキチンリガーゼCRBNの細胞内局在が免疫調整薬IMiDsの薬効に及ぼす影響

    徳山 遥香, 片山 美樹, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2017  2017.1 

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  • ターゲット因子の解析を基盤とする生物活性物質が示す作用機構の解明

    坂本 聡, 山口 雄輝, 半田 宏

    新学術領域研究「転写サイクル」冬の若手ワークショップ2017  2017.1 

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  • How Pol II termination and 3' processing sites are precisely determined in higher eukaryotes.高等真核生物においてPol IIの転写終結と3'プロセシングの部位はいかにして正確に決定されるのか

    瑞慶覧 安里, 山本 淳一, 山口 雄輝

    第39回日本分子生物学会年会  2016.12 

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  • NELFを中心としたポリ(A)付加部位選択のメカニズム

    瑞慶覧 安里, 山本 淳一, 山口 雄輝

    第39回日本分子生物学会年会  2016.12 

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  • 多発性骨髄腫における Pomalidomide 標的因子の網羅的探索

    舘野 峻平, 飯田 緑, 藤井 聡, 佐倉 絵里, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2017  2017.1 

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  • リガンド依存的ユビキチンリガーゼCRBNの制御機構

    伊藤 拓水, 朝妻 知子, 山本 淳一, 安藤 秀樹, 佐藤 智美, 山口 雄輝, 半田 宏

    日本ケミカルバイオロジー学会第11回年会  2016.6 

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  • 高等真核生物においてPOL Ⅱの転写終結と3'プロセシングの部位はいかにして正確に決定されるのか

    瑞慶覧 安里, 長谷川 冴妃子, 館野 峻平, 山本 淳一, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2016  2016.9 

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  • TBP類似因子TLPによるDNA損傷応答時の転写抑制と細胞死誘導機構の解析

    鈴木 秀文, 前田 亮, 浦 聖恵, 木村 宏, 山口 雄輝, 田村 隆明

    新学術領域研究「転写サイクル」班会議2016  2016.9 

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  • NELFを中心としたポリ(A)付加部位選択のメカニズム

    瑞慶覧 安里, 舘野 峻平, 山本 淳一, 山口 雄輝

    新学術領域研究「転写サイクル」班会議2016  2016.9 

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  • マウスES細胞における2細胞期特異的な遺伝子の発現制御メカニズムの解析

    鈴木 翔子, 柴田 紘孝, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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  • サリドマイドの多様な薬理作用の分子メカニズム

    山口 雄輝, 伊藤 巧水, 山本 淳一, 半田 宏

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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  • snRNA3'末端プロセシング因子インテグレーターの構造・機能解析

    外山 黛, 荻原 裕里, Thiengtrong Benjarat, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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  • CRBNに対するサリドマイド光学異性体の結合基盤解析

    坂本 聡, 伊藤 拓水, 森 智行, 安藤 秀樹, 山口 雄輝, 箱嶋 敏雄, 半田 宏

    日本ケミカルバイオロジー学会第11回年会  2016.6 

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  • NELFを中心としたRNAの品質管理のメカニズム Invited

    瑞慶覧 安里, 山本 淳一, 磯部 智康, 山口 雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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  • サリドマイド標的タンパク質CRBNの相互作用因子の探索

    徳山 遥香, 新垣 貴之, 山口雄輝

    新学術領域研究「転写サイクル」冬の若手ワークショップ2016  2016.2 

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Industrial property rights

  • CRBNモジュレーターの薬効を高める補助薬のスクリーニング方法

    山口 雄輝, 舘野 峻平, 片山 美樹, 半田 宏

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    Application no:特願2018-93652  Date applied:2018.5

    Announcement no:特開2019-198254  Date announced:2019.11

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  • 骨、関節又は歯異常症の治療物質のスクリーニング方法

    今井 剛, 半田 宏, 山口 雄輝

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    Application no:特願2012-140671  Date applied:2012.6

    Announcement no:特開2013-188201  Date announced:2013.9

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  • 相乗的抗糖尿病治療剤

    今井 剛, 半田 宏, 山口 雄輝

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    Application no:特願2012-108729  Date applied:2012.5

    Announcement no:特開2013-234159  Date announced:2013.11

    Patent/Registration no:特許第6015903号  Date issued:2016.10

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Awards

  • 東工大教育優秀賞

    2019.2  

    山口 雄輝

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  • Tejima Memorial Research Award (for outstanding Ph.D. thesis)

    2000  

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  • Amersham Pharmacia Biotech & Science Prize

    2000  

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  • 手島記念研究賞 (博士論文賞)

    2000  

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    Country:Japan

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  • Amersham Pharmacia Biotech & Science賞

    2000  

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Research Projects

  • Structure-function analysis of transcription elongation/termination complexes using a new method capable of analyzing multifactor complexes

    Grant number:24K02003  2024.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\18590000 ( Direct Cost: \14300000 、 Indirect Cost:\4290000 )

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  • Elucidation of the selection mechanism of transcription termination and polyadenylation sites by using novel proteomic approach

    Grant number:20H03182  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Yamaguchi Yuki

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    Grant amount:\17680000 ( Direct Cost: \13600000 、 Indirect Cost:\4080000 )

    The purpose of this study was to elucidate the selection mechanism of transcription termination and 3' processing sites from the viewpoints of both "reaction field (structure)" and "function." For the former, we analyzed the structural aspect using our proximity-dependent biotinylation method using antibodies. For the latter, we analyzed the effects of knockdown of candidate factors and 1,6-hexanediol treatment on alternative polyadenylation by RNA-seq. These results revealed that transcription and RNA processing factors such as NELF, CBC, and CF-Im cooperate with Cajal Body components to regulate alternative polyadenylation in many genes.

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  • Elucidation of the mechanism of mitochondrial disease cell death inhibition and drug discovery

    Grant number:20H03648  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Osaka Hitoshi

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    Grant amount:\17680000 ( Direct Cost: \13600000 、 Indirect Cost:\4080000 )

    We found that apomorphine inhibits BSO-induced cell death by inhibiting ferotosis and, as a molecular mechanism, binds to and activates the enzyme X, reducing NADH stress seen in mitochondrial diseases and improving mitochondrial function. Furthermore, since the ferotosis inhibitory effect of apomorphine is different from that of dopamine agonists, we synthesized and explored apomorphine derivatives without dopamine receptor binding ability, and created a number of ferotosis inhibitors with reduced side effects caused by dopamine agonist activity. The research results were compiled and a patent application was filed.

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  • Search for novel modulators of cereblon, the target of thalidomide that regulates neural stem cell proliferation and deifferentiation

    Grant number:17H06112  2017.5 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (S)  Grant-in-Aid for Scientific Research (S)

    HANDA Hiroshi

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    Grant amount:\181090000 ( Direct Cost: \139300000 、 Indirect Cost:\41790000 )

    We demonstrated that cereblon (CRBN), which is a target of thalidomide, plays an important role in brain development via the proliferation and differentiation of neural stem cells. We also identified p63 as a novel substrate of CRBN, which is involved in thalidomide teratogenicity. We synthesized more than dozens of thalidomide derivatives, called CRBN modulators, in which fluorine or hetero-functional groups were introduced at various positions on their aromatic ring. We identified 4 excellent candidate compounds that increase the proliferation of neural stem cells using two model systems, i.e., zebrafish embryos and human iPS-derived stem cell culture. Thus, it has become clear that this approach to drug discovery from considering the molecular structure is effective. In addition, we searched and identified factors regulating the efficacy of CRBN modulators, which lead to the establishment of an infrastructure for the application of novel CRBN modulators to clinical medicine.

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  • Elucidation of control mechanisms of transcriptional checkpoint during Pol II elongation, termination, and recycle

    Grant number:24118002  2012.6 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    YAMAGUCHI Yuki, NISHIYAMA Akira, NAKABAYASHI Jun, ISOBE Tomoyasu, YAMAMOTO Junichi, KATO Junko, SUZUKI Hidefumi, SOU Seifuku, SHIBATA Hirotaka, TATENO Shumpei, HASEGAWA Sakiko, ARAKAKI Takayuki, ZUKERAN Ari, KUROTAKI Daisuke, BAN Tatsuma, FUSHIMI Kentaro

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    Grant amount:\224250000 ( Direct Cost: \172500000 、 Indirect Cost:\51750000 )

    Synthesis of full-length RNAs is made possible through multiple interactions of Pol II with DNA, RNA, and proteins (e.g., chromatin factors, transcription initiation factors, elongation factors, termination factors, and RNA processing factors), which together form a large complex that undergoes rapid remodeling during the transcription cycle. However, the detail of this dynamic process remains poorly understood. Here we set out to explore mechanisms for the remodeling of the Pol II-containing complex during the transcription cycle and regulatory checkpoints in it, through identification and characterization of new Pol II-interacting factors and kinetic analyses in living cells.

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  • Promotion of the Transcription Cycle Area

    Grant number:24118001  2012.6 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    YAMAGUCHI Yuki, ISHI Shunsuke, TANAKA Kiyoji, HIROSE Susumu, SHIOMI Haruhiko, SATO Fumitoshi

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    Grant amount:\119340000 ( Direct Cost: \91800000 、 Indirect Cost:\27540000 )

    The goal of the Transcription Cycle Area is to gain an integrative perspective on multiple steps and layers of transcription using “high-resolution approaches,” in which leading edge technology and computational science are combined with conventional methodology. To facilitate research activity of the area toward this goal, the following support programs were conducted as planned: (1) Establishment and management of the Transcription Cycle Core Facility. (2) Promotion of cooperation within the Area and with outside groups. (3) Support of young researchers. (4) Public relations.

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  • Integral understanding of the mechanism of transcription cycle through quantitative, high-resolution approaches

    Grant number:3408  2012.6 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

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  • Regulation of fate-determination of RNA and role of transcriptional machinery in heterochromatin formatin

    Grant number:20052013  2008 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Priority Areas  Grant-in-Aid for Scientific Research on Priority Areas

    MURAKAMI Yota

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    Grant amount:\28000000 ( Direct Cost: \28000000 )

    mRNA and non-coding RNA, both of which are transcribed by RNA polymerase II, have different fate with different RNA processing processes. We analyzed the mechanism for the fate-determination mechanism and found that transcriptional elongation factors were involved in fate-determination process of heterochromatic ncRNA in fission yeast. We also found that fission yeast heterochromatin ncRNA formed DNA:RNA hybrid to remain on chromatin and plays a role in heterochromatin formation. In addition, we revealed the mechanism to regulate elongation of transcription by transcriptional elongation factors.

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  • 生細胞内(insitu)でタンパク質間の相互作用を解析・同定する新規な方法の開発

    Grant number:18770148  2006 - 2007

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    山口 雄輝

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    Grant amount:\3600000 ( Direct Cost: \3600000 )

    本研究の目的は,生細胞内の目的タンパク質にケミカル(低分子化合物)を導入し,それを利用して近傍の生体分子を同定するという新しい相互作用因子解析法を開発することであり,そのためにまずin vitro のモデル系で検討を行った.転写伸長因子HDAgに,Cys残基を介して光活性化型クロスリンカーAETを導入し, RNAポリメラーゼIIのHDAg結合表面の決定を試みた. RN AポリメラーゼIIは12個のサブユニットからなる.解析の結果,HDAgはRNAポリメラーゼIIのRpblサブユニットのN末端およびRpb2サブユニットのむ末端と特異的にクロスリンクされることが分かった.これらの領域はRNAポリメラーゼIIの立体構造の中でクランプと呼ばれるドメインに相当することから, HDAgはRNAポリメラーゼIIのクランプに結合すると考えられ,転写伸長因子の作用を理解する上で重要な知見が得られた(Yamaguchiら2007).
    引き続いてin vivo の検討を行なったが,技術的な困難に直面し,期間内に有意義な成果を挙げることができなかった.そこで,これと平行して進めた研究の成果を代わりに報告する.アトラジンは世界で最も多く使われる除草剤の1つだが,植物だけでなく動物に対しても生殖器系などに悪影響を及ぼすことが指摘されている.アトラジンのこうした作用の分子機構を理解するため,アフィニティクロマトグラフィーの手法によりアトラジン結合タンパク質を探索したところ,ミトコンドリアのFIFO-ATP合成酵素が同定された.アトラジンは精子の運動性低下を引き起こすことが知られていたので,それについて調べたところ,アトラジンはFIFO-ATP合成酵素を阻害し,細胞内のATPプールを減少させることで,精子の運動性低下を引き起こすことは判明した(Haseら2008)

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  • 遺伝情報発現を転写伸長段階で制御するDECODE複合体の機能・構造解析

    Grant number:17054014  2005 - 2007

    日本学術振興会  科学研究費助成事業 特定領域研究  特定領域研究

    和田 忠士, 濡木 理, 山口 雄輝, 半田 宏

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    Grant amount:\29900000 ( Direct Cost: \29900000 )

    mRNA合成速度を可変するDECODE複合体は、細胞の発生や分化、癌化過程に関与する。その複合体は、情報読み取り速度を可変することでDECODE回路への情報の流れを制御する。具体的には、転写伸長因子DSIFとNELFによって構成され、キナーゼP-TEFbがセリン・スレオニンのリン酸化でON/0FF活性を調節する。今年度は、試験管内転写実験によりモデル転写因子Ga14-VP16による転写反応の活性化にDSIFとP-TEFbが必須で、DSIFは伸長反応中のRNAポリメラーゼIIの一時停止を回(ポジティブ効果)することを明らかにした。またDSIFのサブユニットの一つであるゼブラフィッシュzSpt5のモルフォリノオリゴによる発現抑制を行い、マイクロアレイを用いた網羅的遺伝子発現解析から赤血球特異的転写因子gata1の発現が低下することがわり、in situハイブリダイゼーション法とレスキュー実験により、gata1遺伝子の発現上昇はDSIFのポジティブ効果に依存することを明らかにした。今年度は、NElF-Aノックアウトマウスの解析を引き続き行った。-/-マウスは早期の胎性致死となるが、そこから単離した-/-ES細胞はfeeder上で増殖することが前年度までに明らかとなったので、NELFが細胞の分化過程に関与するとの予想をたて、ES細胞の多分化能をin vitro分化系により検討した。その結果、-/-細胞では調べた多くの組織特異的マーカーが誘導発現されないことが分かった。ES細胞では繊維芽細胞などの分化した細胞と較べて、転写開始後に制御されている遺伝子が多いことが他のグループによって報告されており、そういった知見も考え合わせると、NELFが特定の分化過程というよりも、もっと根本的な過程-多能性細胞が分化に踏み出す最初のステップーに寄与しているのではないかと考えられる。

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  • ノックアウトマウスを用いた基本転写伸長因子の生理機能の解明

    Grant number:15770107  2003 - 2004

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    山口 雄輝

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    Grant amount:\3000000 ( Direct Cost: \3000000 )

    NELFはRNAポリメラーゼIIによる転写伸長を抑制することが知られる唯一の因子である.NELFの個体レベルでの機能を明らかにするため,NELFの4つのサブユニットのうち2つの遺伝子を破壊したマウスを作製した.NELF-E欠損マウスは一見正常に誕生し生育した.一方,NELF-A欠損マウスはE10.5以前で耐性致死となった.よく調べたところ,NELF-E欠損マウスはNELF-EのC末端側の約2/3を欠損したトランケート型タンパク質を発現していた.このC末端部分には,機能的に重要と考えていたRNA結合ドメインRRMが含まれる.NELF-Eの欠損がnullでないため断定はできないものの,以上の結果は,個体レベルでの生存に関してNELFの2つのサブユニットが対照的な要求性を示すという予想外の可能性を示した.NELF-A欠損マウスについて詳しく調べたところ,E8.5の段階で-/-変異体がメンデル律に則って見つかった.ただし,それらは一見するとE6.5に相当するような小さな胚(あるいは吸収途中と思われる残骸組織)であり,組織学的解析もそれを裏付けた.in situハイブリダイゼーションの結果によれば,NELF-Aは少なくともE8.5以降の段階で様々な組織に発現していた.以上の結果はNELFの要求性が極めて発生段階特異的に現れることを示しており,大変興味深い.そもそもNELFは転写を普遍的に制御する因子として我々が同定した.初期発生の過程で転写は2細胞期から始まっているわけだが,NELF-Aがなくても着床(E4.5)まで問題なく進み,E6.5あたりで突如として発達遅滞が引き起こされるという今回の結果は,我々にとって意外であり,NELFの遺伝子特異的な働きを明確に示すものと考えている.

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  • RNAポリメラーゼ2による転写伸長反応制御の分子機構

    Grant number:99J06444  1999 - 2000

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    山口 雄輝

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    Grant amount:\2400000 ( Direct Cost: \2400000 )

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  • Study on the role of transcriptional elongation control in the expression of cellular functions

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    Grant type:Competitive

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  • 転写伸長反応の制御を介した細胞機能発現機構の解明

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    Grant type:Competitive

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