Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes.

Abstract:

BACKGROUND:DNA methylation and the Polycomb repression system are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. RESULTS:By genome-wide mapping of the Polycomb Repressive Complex 2-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and Polycomb Repressive Complex 2 from Polycomb target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. CONCLUSIONS:An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining Polycomb Repressive Complex 2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.

journal_name

Genome Biol

journal_title

Genome biology

authors

Reddington JP,Perricone SM,Nestor CE,Reichmann J,Youngson NA,Suzuki M,Reinhardt D,Dunican DS,Prendergast JG,Mjoseng H,Ramsahoye BH,Whitelaw E,Greally JM,Adams IR,Bickmore WA,Meehan RR

doi

10.1186/gb-2013-14-3-r25

subject

Has Abstract

pub_date

2013-03-25 00:00:00

pages

R25

issue

3

eissn

1474-7596

issn

1474-760X

pii

gb-2013-14-3-r25

journal_volume

14

pub_type

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