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.

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

  • 1,468
    Page views
  • 220
    Downloads
  • 13
    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)

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

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

  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

Further reading

    1. Structural Biology and Molecular Biophysics
    Christopher M Hoel, Lin Zhang, Stephen G Brohawn
    Research Article Updated

    TMEM87s are eukaryotic transmembrane proteins with two members (TMEM87A and TMEM87B) in humans. TMEM87s have proposed roles in protein transport to and from the Golgi, as mechanosensitive ion channels, and in developmental signaling. TMEM87 disruption has been implicated in cancers and developmental disorders. To better understand TMEM87 structure and function, we determined a cryo-EM structure of human TMEM87A in lipid nanodiscs. TMEM87A consists of a Golgi-dynamics (GOLD) domain atop a membrane-spanning seven-transmembrane helix domain with a large cavity open to solution and the membrane outer leaflet. Structural and functional analyses suggest TMEM87A may not function as an ion channel or G-protein coupled receptor. We find TMEM87A shares its characteristic domain arrangement with seven other proteins in humans; three that had been identified as evolutionary related (TMEM87B, GPR107, and GPR108) and four previously unrecognized homologs (GPR180, TMEM145, TMEM181, and WLS). Among these structurally related GOLD domain seven-transmembrane helix (GOST) proteins, WLS is best characterized as a membrane trafficking and secretion chaperone for lipidated Wnt signaling proteins. We find key structural determinants for WLS function are conserved in TMEM87A. We propose TMEM87A and structurally homologous GOST proteins could serve a common role in trafficking membrane-associated cargo.

    1. Immunology and Inflammation
    2. Structural Biology and Molecular Biophysics
    Rui Liu, Kangcheng Song ... Lei Chen
    Research Article Updated

    Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions that participate in pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the physiological importance of this complex, its structure remains elusive. Here, we reported the cryo-EM structure of the functional human NOX2-p22 complex in nanodisc in the resting state. NOX2 shows a canonical 6-TM architecture of NOX and p22 has four transmembrane helices. M3, M4, and M5 of NOX2, and M1 and M4 helices of p22 are involved in the heterodimer formation. Dehydrogenase (DH) domain of NOX2 in the resting state is not optimally docked onto the transmembrane domain, leading to inefficient electron transfer and NADPH binding. Structural analysis suggests that the cytosolic factors might activate the NOX2-p22 complex by stabilizing the DH in a productive docked conformation.