The Polycomb group protein EZH2 directly controls DNA methylation.

Article Details

Citation

Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F

The Polycomb group protein EZH2 directly controls DNA methylation.

Nature. 2006 Feb 16;439(7078):871-4. Epub 2005 Dec 14.

PubMed ID
16357870 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
DNA (cytosine-5)-methyltransferase 1P26358Details
Histone-lysine N-methyltransferase EZH2Q15910Details
DNA (cytosine-5)-methyltransferase 3AQ9Y6K1Details
DNA (cytosine-5)-methyltransferase 3BQ9UBC3Details