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

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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) 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.

Original languageEnglish (US)
Pages (from-to)871-874
Number of pages4
JournalNature
Volume439
Issue number7078
DOIs
StatePublished - Feb 16 2006
Externally publishedYes

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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