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 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.
authors.affiliation: Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Viré
authors.forename: Carmen
authors.initials: C
authors.lastname: Brenner
authors.forename: Rachel
authors.initials: R
authors.lastname: Deplus
authors.forename: Loïc
authors.initials: L
authors.lastname: Blanchon
authors.forename: Mario
authors.initials: M
authors.lastname: Fraga
authors.forename: Céline
authors.initials: C
authors.lastname: Didelot
authors.forename: Lluis
authors.initials: L
authors.lastname: Morey
authors.forename: Aleyde
authors.initials: A
authors.lastname: Van Eynde
authors.forename: David
authors.initials: D
authors.lastname: Bernard
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Vanderwinden
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.forename: François
authors.initials: F
authors.lastname: Fuks
mesh_terms: D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000145:classification* / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000145:classification* / Q000378:metabolism*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000145:classification* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004248:DNA (Cytosine-5-)-Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2