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Bivalent chromatin domains in ovarian tumours at initial presentation identify genes predisposed to DNA hypermethylation during acquired resistance to chemotherapy

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107931 | GEO | 2018/08/09

REPOSITORIES: GEO

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Bivalent chromatin domains in ovarian tumours at initial presentation identify genes predisposed to DNA hypermethylation during acquired resistance to chemotherapy [ChIP-seq]

Project description:We have used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3 associated chromatin in primary high-grade serous ovarian carcinoma and normal ovarian surface and fallopian tube tissue. Sets of genes with proximal bivalent marks were defined using this data and subsequently evaluated as signatures of systematic change in DNA methylation and gene expression between pairs of tissue samples taken from patients at primary presentation and relapse following chemotherapy. Gene expression microarrays from primary tumours were used to assess transcriptional associations of chromatin marks identified in tumours through ChIP-seq

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Bivalent chromatin domains in ovarian tumours at initial presentation identify genes predisposed to DNA hypermethylation during acquired resistance to chemotherapy

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Project description:There is a growing realization that some aging-associated phenotypes/diseases have an epigenetic basis. Here we report the first genome-scale study of epigenomic dynamics during normal human aging. We identify aging-associated differentially methylated regions (aDMRs) in whole blood in a discovery cohort, and then replicate these aDMRs in sorted CD4+ T-cells and CD14+ monocytes in an independent cohort, suggesting that aDMRs occur in precursor haematopoietic cells. Further replication of the aDMRs in buccal cells, representing a tissue that originates from a different germ-layer compared with blood, demonstrates that the aDMR signature is a multi-tissue phenomenon. Moreover, we demonstrate that aging-associated DNA hypermethylation occurs predominantly at bivalent chromatin domain promoters. This same category of promoters, associated with key developmental genes, is frequently hypermethylated in cancers and in vitro cell culture, pointing to a novel mechanistic link between aberrant hypermethylation in cancer, aging, and cell culture. We measured the methylation state of 27,578 CpG sites (Illumina HumanMethylation27 array) in sorted human blood cells to validate aging-associated DMRs.

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