Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19

  1. Cheng Dong
  2. Reiko Nakagawa
  3. Kyohei Oyama
  4. Yusuke Yamamoto
  5. Weilian Zhang
  6. Aiping Dong
  7. Yanjun Li
  8. Yuriko Yoshimura
  9. Hiroyuki Kamiya
  10. Jun-ichi Nakayama
  11. Jun Ueda
  12. Jinrong Min  Is a corresponding author
  1. Tianjin Medical University, China
  2. RIKEN, Japan
  3. Asahikawa Medical University, Japan
  4. University of Toronto, Canada
  5. National Institute for Basic Biology, Japan
  6. National Institute of Basic Biology, Japan

Abstract

The PRC2 (Polycomb repressive complex 2) complex is a multi-component histone H3K27 methyltransferase, best known for silencing Hox genes during embryonic development. The Polycomb-like proteins PHF1, MTF2 and PHF19 are critical components of PRC2 by stimulating its catalytic activity in embryonic stem (ES) cells. The Tudor domains of PHF1/19 have been previously shown to be readers of H3K36me3 in vitro. However, some other studies suggest that PHF1 and PHF19 co-localize with the H3K27me3 mark, but not H3K36me3 in cells. Here, we provide further evidence that PHF1 co-localizes with H3t in testis, and its Tudor domain preferentially binds to H3tK27me3 over canonical H3K27me3 in vitro. Our complex structures of the Tudor domains of PHF1 and PHF19 with H3tK27me3 shed light on the molecular basis for preferential recognition of H3tK27me3 by PHF1 and PHF19 over canonical H3K27me3, implicating that H3tK27me3 might be a physiological ligand of PHF1/19.

Data availability

Diffraction data have been deposited in PDB under the accession codes 6WAT, 6WAU, 6WAV

The following data sets were generated

Article and author information

Author details

  1. Cheng Dong

    Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Reiko Nakagawa

    Laboratory for Phyloinformatics, RIKEN, Kobe, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6178-2945
  3. Kyohei Oyama

    Department of Cardiac Surgery, Asahikawa Medical University, Asahikawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Yusuke Yamamoto

    Department of Cardiac Surgery, Asahikawa Medical University, Asahikawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Weilian Zhang

    Structural Genomics Consortium, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Aiping Dong

    Structural Genomics Consortium, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Yanjun Li

    Structural Genomics Consortium, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Yuriko Yoshimura

    Division of Chromatin Regulation, National Institute for Basic Biology, Okazaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Hiroyuki Kamiya

    Department of Cardiac Surgery, Asahikawa Medical University, Asahikawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
  10. Jun-ichi Nakayama

    Division of Chromatin Regulation, National Institute of Basic Biology, Okazaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  11. Jun Ueda

    Centre for Advanced Research and Education, Asahikawa Medical University, Asahikawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
  12. Jinrong Min

    Structural Genomics Consortium, University of Toronto, Toronto, Canada
    For correspondence
    jr.min@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5210-3130

Funding

National Natural Science Foundation of China (31900865)

  • Cheng Dong

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Dong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Cheng Dong
  2. Reiko Nakagawa
  3. Kyohei Oyama
  4. Yusuke Yamamoto
  5. Weilian Zhang
  6. Aiping Dong
  7. Yanjun Li
  8. Yuriko Yoshimura
  9. Hiroyuki Kamiya
  10. Jun-ichi Nakayama
  11. Jun Ueda
  12. Jinrong Min
(2020)
Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19
eLife 9:e58675.
https://doi.org/10.7554/eLife.58675

Share this article

https://doi.org/10.7554/eLife.58675

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