The Polycomb group protein EZH2 directly controls DNA methylation.
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.
Viré
Emmanuelle
E
Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, 808 route de Lennik, 1070 Brussels, Belgium.
Brenner
Carmen
C
Deplus
Rachel
R
Blanchon
Loïc
L
Fraga
Mario
M
Didelot
Céline
C
Morey
Lluis
L
Van Eynde
Aleyde
A
Bernard
David
D
Vanderwinden
Jean-Marie
JM
Bollen
Mathieu
M
Esteller
Manel
M
Di Croce
Luciano
L
de Launoit
Yvan
Y
Fuks
François
F
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*
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