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

Abstract

The tumor suppressor p53 functions as a pioneer transcription factor that binds a nucleosomal target DNA sequence. However, the mechanism by which p53 binds to its target DNA in the nucleosome remains elusive. Here we report the cryo-electron microscopy structures of the p53 DNA-binding domain and the full-length p53 protein complexed with a nucleosome containing the 20 base-pair target DNA sequence of p53 (p53BS). In the p53-nucleosome structures, the p53 DNA-binding domain forms a tetramer and specifically binds to the p53BS DNA, located near the entry/exit region of the nucleosome. The nucleosomal position of the p53BS DNA is within the genomic p21 promoter region. The p53 binding peels the DNA from the histone surface, and drastically changes the DNA path around the p53BS on the nucleosome. The C-terminal domain of p53 also binds to the DNA around the center and linker DNA regions of the nucleosome, as revealed by hydroxyl radical footprinting. These results provide important structural information for understanding the mechanism by which p53 binds the nucleosome and changes the chromatin structure for gene activation.

DOI： 10.1093/pnasnexus/pgac177

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Other Link： https://academic.oup.com/pnasnexus/article-pdf/1/4/pgac177/47088078/pgac177.pdf

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Cold Spring Harbor Laboratory  

<title>Abstract</title>The canonical nucleosome, which represents the predominant packaging unit in eukaryotic chromatin, has an octameric core made up of two histone H2A-H2B and H3-H4 dimers with ~147 base-pair (bp) DNA wrapping around it. Non-nucleosome particles with alterative histone stoichiometries and DNA wrapping configurations have been found, and they could profoundly influence genome architecture and function. Here we solved the structure of the H3-H4 octasome, which is a nucleosome-like particle with a core made up of four H3-H4 dimers. Two conformations, open and closed, are determined at 3.9 Å and 3.6 Å resolutions by cryo-electron microscopy, respectively. The H3-H4 octasome, made up of a di-tetrameric core, is wrapped by ~120 bp DNA in 1.5 negative superhelical turns. The symmetrical halves are connected by a unique H4-H4’ interface along the dyad axis. <italic>In vivo</italic> crosslinking of cysteine probes placed at another unique H3-H3’ interface demonstrated the existence of the H3-H4 octasome in cells.

DOI： 10.1101/2021.10.27.466091

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

<title>Abstract</title>
The tumour suppressor protein p53 regulates various genes involved in cell-cycle arrest, apoptosis and DNA repair in response to cellular stress, and apparently functions as a pioneer transcription factor. The pioneer transcription factors can bind nucleosomal DNA, where many transcription factors are largely restricted. However, the mechanisms by which p53 recognizes the nucleosomal DNA are poorly understood. In the present study, we found that p53 requires linker DNAs for the efficient formation of p53-nucleosome complexes. p53 forms an additional specific complex with the nucleosome, when the p53 binding sequence is located around the entry/exit region of the nucleosomal DNA. We also showed that p53 directly binds to the histone H3-H4 complex via its N-terminal 1–93 amino acid region. These results shed light on the mechanism of nucleosome recognition by p53.

DOI： 10.1093/jb/mvaa081

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Other Link： http://academic.oup.com/jb/article-pdf/168/6/669/35149042/mvaa081.pdf

Language：Japanese   Publishing type：Research paper (international conference proceedings)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Biophysical Society of Japan  

DOI： 10.2142/biophysico.15.0_251

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

DOI： 10.1038/nature22328

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

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Publishing type：Research paper (bulletin of university, research institution)  

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Language：English   Publishing type：Research paper (bulletin of university, research institution)  

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

DOI： 10.1016/j.jmb.2016.01.028

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

DOI： 10.1093/nar/gkt010

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

DOI： 10.1271/bbb.110653

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Language：Japanese   Publishing type：Doctoral thesis  

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

Scopus

PubMed

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

DOI： 10.1038/nature07611

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

DOI： 10.1073/pnas.0801950105

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