title: 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.
authors.forename: James P
authors.initials: JP
authors.lastname: Reddington
authors.forename: Sara M
authors.initials: SM
authors.lastname: Perricone
authors.forename: Colm E
authors.initials: CE
authors.lastname: Nestor
authors.forename: Judith
authors.initials: J
authors.lastname: Reichmann
authors.forename: Neil A
authors.initials: NA
authors.lastname: Youngson
authors.forename: Masako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Diana
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Donncha S
authors.initials: DS
authors.lastname: Dunican
authors.forename: James G
authors.initials: JG
authors.lastname: Prendergast
authors.forename: Heidi
authors.initials: H
authors.lastname: Mjoseng
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Ramsahoye
authors.forename: Emma
authors.initials: E
authors.lastname: Whitelaw
authors.forename: John M
authors.initials: JM
authors.lastname: Greally
authors.forename: Ian R
authors.initials: IR
authors.lastname: Adams
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
authors.forename: Richard R
authors.initials: RR
authors.lastname: Meehan
mesh_terms: D000818:Animals; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008957:Models, Genetic; D005810:Multigene Family; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D006657:Histones; D012097:Repressor Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D063151:Polycomb Repressive Complex 2; D008239:Lysine