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The Polycomb group protein EZH2 directly controls DNA methylation - Nature

  • ️Fuks, François
  • ️Wed Dec 14 2005
  • Letter
  • Published: 14 December 2005

Nature volume 439, pages 871–874 (2006)Cite this article

A Corrigendum to this article was published on 12 April 2007

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.

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Acknowledgements

We thank A. Otte for pGEX-EZH2, E. Li for DNMT3A and DNMT3B immune sera, S. Pradhan for the anti-DNMT1 antibody, and C. Beaudouin for pGEX-PLZF. We thank P. Putmans and H. N. Tran for excellent technical assistance. E.V., C.B., R.D., C.D. and L.B. were supported by the Télévie and the F.N.R.S. L.B. was also supported by the “Fondation pour la Recherche Médicale”. D.B. was supported by a Marie Curie Fellowship. F.F. is a “Chercheur Qualifié du F.N.R.S.”. This work was supported by grants from MEC-Plan Nacional de I + D + I to L.D.C., and from the “Fédération Belge contre le Cancer”, the F.N.R.S, “FB Assurances”, and “A.R.C. de la Communauté Française de Belgique” to Y.d.L. and F.F.

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Authors and Affiliations

  1. Faculty of Medicine, Laboratory of Molecular Virology, Free University of Brussels, 808 route de Lennik, 1070, Brussels, Belgium

    Emmanuelle Viré, Carmen Brenner, Rachel Deplus, Loïc Blanchon, Céline Didelot, David Bernard, Yvan de Launoit & François Fuks

  2. CNIO, Cancer Epigenetics Group, C/- Melchor Fernández Almagro 3, 28029, Madrid, Spain

    Mario Fraga & Manel Esteller

  3. ICREA and CRG, Passeig Maritim 37-49, E-08003, Barcelona, Spain

    Lluis Morey & Luciano Di Croce

  4. Division of Biochemistry, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium

    Aleyde Van Eynde & Mathieu Bollen

  5. Faculty of Medicine, Laboratory of Neurophysiology, Free University of Brussels, 808 route de Lennik, 1070, Brussels, Belgium

    Jean-Marie Vanderwinden

  6. UMR 8117, CNRS, Institut Pasteur de Lille, Université de Lille 1, Institut de Biologie de Lille, 1 rue Calmette, 59021, Cedex, Lille, France

    Yvan de Launoit

Authors

  1. Emmanuelle Viré

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  2. Carmen Brenner

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  3. Rachel Deplus

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  4. Loïc Blanchon

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  5. Mario Fraga

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  6. Céline Didelot

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  7. Lluis Morey

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  8. Aleyde Van Eynde

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  9. David Bernard

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  10. Jean-Marie Vanderwinden

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  11. Mathieu Bollen

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  12. Manel Esteller

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  13. Luciano Di Croce

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  14. Yvan de Launoit

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  15. François Fuks

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Corresponding author

Correspondence to François Fuks.

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Supplementary information

Supplementary Methods

This file contains technical details of experimental methods used in this study. (DOC 25 kb)

Supplementary Figure 1

GST pull-down mapping the interaction between DNMTs and EZH2. (PDF 3367 kb)

Supplementary Figure 2

EED and SUZ12 associate with DNA methyltransferase activity. (PDF 3610 kb)

Supplementary Figure 3

Validation of depletion of endogenous EZH2 or DNMTs by RNAi. (PDF 2998 kb)

Supplementary Figure 4

EZH2 or H3K27me3 binding to MYT1 does not require the presence of DNMTs. (PDF 3031 kb)

Supplementary Figure 5

CpG methylation status analysis of the EZH2-target promoters MYT1 and WNT1 in cells overexpressing EZH2. (PDF 4661 kb)

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Cite this article

Viré, E., Brenner, C., Deplus, R. et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871–874 (2006). https://doi.org/10.1038/nature04431

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  • Received: 06 October 2005

  • Accepted: 15 November 2005

  • Published: 14 December 2005

  • Issue Date: 16 February 2006

  • DOI: https://doi.org/10.1038/nature04431

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