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Epigenetic mechanisms to propagate histone acetylation by p300/CBP

Author

Listed:
  • Masaki Kikuchi

    (RIKEN Center for Biosystems Dynamics Research)

  • Satoshi Morita

    (RIKEN Center for Biosystems Dynamics Research)

  • Masatoshi Wakamori

    (RIKEN Center for Biosystems Dynamics Research)

  • Shin Sato

    (RIKEN Center for Biosystems Dynamics Research)

  • Tomomi Uchikubo-Kamo

    (RIKEN Center for Biosystems Dynamics Research)

  • Takehiro Suzuki

    (Technology Platform Division, RIKEN Center for Sustainable Resource Science)

  • Naoshi Dohmae

    (Technology Platform Division, RIKEN Center for Sustainable Resource Science)

  • Mikako Shirouzu

    (RIKEN Center for Biosystems Dynamics Research)

  • Takashi Umehara

    (RIKEN Center for Biosystems Dynamics Research)

Abstract

Histone acetylation is important for the activation of gene transcription but little is known about its direct read/write mechanisms. Here, we report cryogenic electron microscopy structures in which a p300/CREB-binding protein (CBP) multidomain monomer recognizes histone H4 N-terminal tail (NT) acetylation (ac) in a nucleosome and acetylates non-H4 histone NTs within the same nucleosome. p300/CBP not only recognized H4NTac via the bromodomain pocket responsible for reading, but also interacted with the DNA minor grooves via the outside of that pocket. This directed the catalytic center of p300/CBP to one of the non-H4 histone NTs. The primary target that p300 writes by reading H4NTac was H2BNT, and H2BNTac promoted H2A-H2B dissociation from the nucleosome. We propose a model in which p300/CBP replicates histone N-terminal tail acetylation within the H3-H4 tetramer to inherit epigenetic storage, and transcribes it from the H3-H4 tetramer to the H2B-H2A dimers to activate context-dependent gene transcription through local nucleosome destabilization.

Suggested Citation

  • Masaki Kikuchi & Satoshi Morita & Masatoshi Wakamori & Shin Sato & Tomomi Uchikubo-Kamo & Takehiro Suzuki & Naoshi Dohmae & Mikako Shirouzu & Takashi Umehara, 2023. "Epigenetic mechanisms to propagate histone acetylation by p300/CBP," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39735-4
    DOI: 10.1038/s41467-023-39735-4
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    References listed on IDEAS

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