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Role of the polycomb protein EED in the propagation of repressive histone marks

Author

Listed:
  • Raphael Margueron

    (New York University Medical School, 522 First Avenue, New York, New York 10016, USA)

  • Neil Justin

    (MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK)

  • Katsuhito Ohno

    (Rutgers University, Nelson Laboratories, 604 Allison Road, Piscataway, New Jersey 08854, USA)

  • Miriam L. Sharpe

    (MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK)

  • Jinsook Son

    (New York University Medical School, 522 First Avenue, New York, New York 10016, USA)

  • William J. Drury III

    (New York University Medical School, 522 First Avenue, New York, New York 10016, USA)

  • Philipp Voigt

    (New York University Medical School, 522 First Avenue, New York, New York 10016, USA)

  • Stephen R. Martin

    (MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK)

  • William R. Taylor

    (MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK)

  • Valeria De Marco

    (MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK)

  • Vincenzo Pirrotta

    (Rutgers University, Nelson Laboratories, 604 Allison Road, Piscataway, New Jersey 08854, USA)

  • Danny Reinberg

    (New York University Medical School, 522 First Avenue, New York, New York 10016, USA)

  • Steven J. Gamblin

    (MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK)

Abstract

Polycomb group proteins have an essential role in the epigenetic maintenance of repressive chromatin states. The gene-silencing activity of the Polycomb repressive complex 2 (PRC2) depends on its ability to trimethylate lysine 27 of histone H3 (H3K27) by the catalytic SET domain of the EZH2 subunit, and at least two other subunits of the complex: SUZ12 and EED. Here we show that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2. Mutations in EED that prevent it from recognizing repressive trimethyl-lysine marks abolish the activation of PRC2 in vitro and, in Drosophila, reduce global methylation and disrupt development. These findings suggest a model for the propagation of the H3K27me3 mark that accounts for the maintenance of repressive chromatin domains and for the transmission of a histone modification from mother to daughter cells.

Suggested Citation

  • Raphael Margueron & Neil Justin & Katsuhito Ohno & Miriam L. Sharpe & Jinsook Son & William J. Drury III & Philipp Voigt & Stephen R. Martin & William R. Taylor & Valeria De Marco & Vincenzo Pirrotta , 2009. "Role of the polycomb protein EED in the propagation of repressive histone marks," Nature, Nature, vol. 461(7265), pages 762-767, October.
    • Handle: RePEc:nat:nature:v:461:y:2009:i:7265:d:10.1038_nature08398
    DOI: 10.1038/nature08398
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    Cited by:

    1. Bo Zhang & Chen Zhao & Wenchen Shen & Wei Li & Yue Zheng & Xiangfei Kong & Junbao Wang & Xudong Wu & Tao Zeng & Ying Liu & Yan Zhou, 2023. "KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Cuifang Liu & Juan Yu & Aoqun Song & Min Wang & Jiansen Hu & Ping Chen & Jicheng Zhao & Guohong Li, 2023. "Histone H1 facilitates restoration of H3K27me3 during DNA replication by chromatin compaction," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Allison P. Siegenfeld & Shelby A. Roseman & Heejin Roh & Nicholas Z. Lue & Corin C. Wagen & Eric Zhou & Sarah E. Johnstone & Martin J. Aryee & Brian B. Liau, 2022. "Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Lihu Gong & Xiuli Liu & Lianying Jiao & Xin Yang & Andrew Lemoff & Xin Liu, 2022. "CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Benjamin A. Nacev & Yakshi Dabas & Matthew R. Paul & Christian Pacheco & Michelle Mitchener & Yekaterina Perez & Yan Fang & Alexey A. Soshnev & Douglas Barrows & Thomas Carroll & Nicholas D. Socci & S, 2024. "Cancer-associated Histone H3 N-terminal arginine mutations disrupt PRC2 activity and impair differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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