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 Bioljournal_title
Genome biologyauthors
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 RRdoi
10.1186/gb-2013-14-3-r25subject
Has Abstractpub_date
2013-03-25 00:00:00pages
R25issue
3eissn
1474-7596issn
1474-760Xpii
gb-2013-14-3-r25journal_volume
14pub_type
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