@article{b1154e335e2b4eb3ad768b2eff9b88c2,
title = "The Polycomb group protein EZH2 directly controls DNA methylation",
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.",
author = "Emmanuelle Vir{\'e} and Carmen Brenner and Rachel Deplus and Lo{\"i}c Blanchon and Mario Fraga and C{\'e}line Didelot and Lluis Morey and {Van Eynde}, Aleyde and David Bernard and Vanderwinden, {Jean Marie} and Mathieu Bollen and Manel Esteller and {Di Croce}, Luciano and {De Launoit}, Yvan and Fran{\c c}ois Fuks",
note = "Funding Information: 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 T{\'e}l{\'e}vie and the F.N.R.S. L.B. was also supported by the “Fondation pour la Recherche M{\'e}dicale”. D.B. was supported by a Marie Curie Fellowship. F.F. is a “Chercheur Qualifi{\'e} du F.N.R.S.”. This work was supported by grants from MEC-Plan Nacional de I{\th}D{\th}I to L.D.C., and from the “F{\'e}d{\'e}ration Belge contre le Cancer”, the F.N.R.S, “FB Assurances”, and “A.R.C. de la Communaut{\'e} Franc¸aise de Belgique” to Y.d.L. and F.F.",
year = "2006",
month = feb,
day = "16",
doi = "10.1038/nature04431",
language = "English (US)",
volume = "439",
pages = "871--874",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7078",
}