Bivalent promoter hypermethylation in cancer is linked to the H327me3/H3K4me3 ratio in embryonic stem cells.

BMC Biology
Donnchadh S DunicanRichard R Meehan

Abstract

Thousands of mammalian promoters are defined by co-enrichment of the histone tail modifications H3K27me3 (repressive) and H3K4me3 (activating) and are thus termed bivalent. It was previously observed that bivalent genes in human ES cells (hESC) are frequent targets for hypermethylation in human cancers, and depletion of DNA methylation in mouse embryonic stem cells has a marked impact on H3K27me3 distribution at bivalent promoters. However, only a fraction of bivalent genes in stem cells are targets of hypermethylation in cancer, and it is currently unclear whether all bivalent promoters are equally sensitive to DNA hypomethylation and whether H3K4me3 levels play a role in the interplay between DNA methylation and H3K27me3. We report the sub-classification of bivalent promoters into two groups-promoters with a high H3K27me3:H3K4me3 (hiBiv) ratio or promoters with a low H3K27me3:H3K4me3 ratio (loBiv). HiBiv are enriched in canonical Polycomb components, show a higher degree of local intrachromosomal contacts and are highly sensitive to DNA hypomethylation in terms of H3K27me3 depletion from broad Polycomb domains. In contrast, loBiv promoters are enriched in non-canonical Polycomb components, show lower intrachromosomal contacts...Continue Reading

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Citations

Nov 17, 2020·International Journal of Cancer. Journal International Du Cancer·Rhiannon French, Siim Pauklin
Jan 17, 2021·Protein & Cell·Yuliang FengSiim Pauklin
Mar 17, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Cristina PolicarpiJamie A Hackett

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Datasets Mentioned

BETA
GMEM

Methods Mentioned

BETA
ChIPseq
RRBS
RNAseq
Hi-C
WGBS
Magnetic Activated Cell Sorting
ChIP
PCR

Key Resources (RRID) Mentioned

AB_310624

Software Mentioned

DESeq
Xcaliber
IGV
Picard
BEDTools
bowtie
featureCount
Sequence Read Archive
bowtie2
SRA Toolkit

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