1. Structural Biology and Molecular Biophysics
Download icon

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
Research Article
  • Cited 0
  • Views 614
  • Annotations
Cite this article as: eLife 2020;9:e58675 doi: 10.7554/eLife.58675

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.

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

    Department of Cardiac Surgery, 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.

Reviewing Editor

  1. Xiaobing Shi, Van Andel Institute, United States

Publication history

  1. Received: May 8, 2020
  2. Accepted: August 29, 2020
  3. Accepted Manuscript published: September 1, 2020 (version 1)
  4. Accepted Manuscript updated: September 2, 2020 (version 2)
  5. Version of Record published: September 15, 2020 (version 3)

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.

Metrics

  • 614
    Page views
  • 106
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Structural Biology and Molecular Biophysics
    Sunbin Deng et al.
    Research Article Updated

    NatB is one of three major N-terminal acetyltransferase (NAT) complexes (NatA-NatC), which co-translationally acetylate the N-termini of eukaryotic proteins. Its substrates account for about 21% of the human proteome, including well known proteins such as actin, tropomyosin, CDK2, and α-synuclein (αSyn). Human NatB (hNatB) mediated N-terminal acetylation of αSyn has been demonstrated to play key roles in the pathogenesis of Parkinson's disease and as a potential therapeutic target for hepatocellular carcinoma. Here we report the cryo-EM structure of hNatB bound to a CoA-αSyn conjugate, together with structure-guided analysis of mutational effects on catalysis. This analysis reveals functionally important differences with human NatA and Candida albicans NatB, resolves key hNatB protein determinants for αSyn N-terminal acetylation, and identifies important residues for substrate-specific recognition and acetylation by NatB enzymes. These studies have implications for developing small molecule NatB probes and for understanding the mode of substrate selection by NAT enzymes.

    1. Structural Biology and Molecular Biophysics
    Zoe L Watson et al.
    Research Article

    Using cryo-electron microscopy (cryo-EM), we determined the structure of the Escherichia coli 70S ribosome with a global resolution of 2.0 Å. The maps reveal unambiguous positioning of protein and RNA residues, their detailed chemical interactions, and chemical modifications. Notable features include the first examples of isopeptide and thioamide backbone substitutions in ribosomal proteins, the former likely conserved in all domains of life. The maps also reveal extensive solvation of the small (30S) ribosomal subunit, and interactions with A-site and P-site tRNAs, mRNA, and the antibiotic paromomycin. The maps and models of the bacterial ribosome presented here now allow a deeper phylogenetic analysis of ribosomal components including structural conservation to the level of solvation. The high quality of the maps should enable future structural analysis of the chemical basis for translation and aid the development of robust tools for cryo-EM structure modeling and refinement.