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 #
Nature Publishing Group
Nature vol:439 issue:7078 pages:871-4
The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation 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.