The Polycomb group protein EZH2 directly controls DNA methylation

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 Esteller; Luciano Di Croce; Yvan De Launoit; François Fuks

doi:10.1038/nature04431

The Polycomb group protein EZH2 directly controls DNA methylation

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 Esteller, Luciano Di Croce, Yvan De Launoit, François Fuks

Research output: Contribution to journal › Article

1494 Scopus citations

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) proteins^2,3 and the DNA methylation ^4,5 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.

Original language	English (US)
Pages (from-to)	871-874
Number of pages	4
Journal	Nature
Volume	439
Issue number	7078
DOIs	https://doi.org/10.1038/nature04431
State	Published - Feb 16 2006
Externally published	Yes

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Viré, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J. M., Bollen, M., Esteller, M., Di Croce, L., De Launoit, Y., & Fuks, F. (2006). The Polycomb group protein EZH2 directly controls DNA methylation. Nature, 439(7078), 871-874. https://doi.org/10.1038/nature04431

The Polycomb group protein EZH2 directly controls DNA methylation. / Viré, Emmanuelle; Brenner, Carmen; Deplus, Rachel; Blanchon, Loïc; Fraga, Mario; Didelot, Céline; Morey, Lluis; Van Eynde, Aleyde; Bernard, David; Vanderwinden, Jean Marie; Bollen, Mathieu; Esteller, Manel; Di Croce, Luciano; De Launoit, Yvan; Fuks, François.

In: Nature, Vol. 439, No. 7078, 16.02.2006, p. 871-874.

Research output: Contribution to journal › Article

Viré, Emmanuelle ; Brenner, Carmen ; Deplus, Rachel ; Blanchon, Loïc ; Fraga, Mario ; Didelot, Céline ; Morey, Lluis ; Van Eynde, Aleyde ; Bernard, David ; Vanderwinden, Jean Marie ; Bollen, Mathieu ; Esteller, Manel ; Di Croce, Luciano ; De Launoit, Yvan ; Fuks, François. / The Polycomb group protein EZH2 directly controls DNA methylation. In: Nature. 2006 ; Vol. 439, No. 7078. pp. 871-874.

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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 methylation 4,5 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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AU - Bollen, Mathieu

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AU - Fuks, François

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N2 - 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 methylation 4,5 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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