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The Polycomb group protein EZH2 directly controls DNA methylation

Author

Listed:
  • Emmanuelle Viré

    (Free University of Brussels)

  • Carmen Brenner

    (Free University of Brussels)

  • Rachel Deplus

    (Free University of Brussels)

  • Loïc Blanchon

    (Free University of Brussels)

  • Mario Fraga

    (CNIO, Cancer Epigenetics Group)

  • Céline Didelot

    (Free University of Brussels)

  • Lluis Morey

    (ICREA and CRG)

  • Aleyde Van Eynde

    (Katholieke Universiteit Leuven)

  • David Bernard

    (Free University of Brussels)

  • Jean-Marie Vanderwinden

    (Free University of Brussels)

  • Mathieu Bollen

    (Katholieke Universiteit Leuven)

  • Manel Esteller

    (CNIO, Cancer Epigenetics Group)

  • Luciano Di Croce

    (ICREA and CRG)

  • Yvan de Launoit

    (Free University of Brussels
    Université de Lille 1, Institut de Biologie de Lille)

  • François Fuks

    (Free University of Brussels)

Abstract

The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function1. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins2,3 and the DNA methylation4,5 systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts—within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)—with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.

Suggested Citation

  • Emmanuelle Viré & Carmen Brenner & Rachel Deplus & Loïc Blanchon & Mario Fraga & Céline Didelot & Lluis Morey & Aleyde Van Eynde & David Bernard & Jean-Marie Vanderwinden & Mathieu Bollen & Manel Este, 2006. "The Polycomb group protein EZH2 directly controls DNA methylation," Nature, Nature, vol. 439(7078), pages 871-874, February.
    • Handle: RePEc:nat:nature:v:439:y:2006:i:7078:d:10.1038_nature04431
    DOI: 10.1038/nature04431
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