Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Human Aging-associated DNA Hypermethylation Occurs Preferentially at Bivalent Chromatin Domains

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Owen McCann

PROVIDER: E-GEOD-20242 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains.

Rakyan Vardhman K VK Down Thomas A TA Maslau Siarhei S Andrew Toby T Yang Tsun-Po TP Beyan Huriya H Whittaker Pamela P McCann Owen T OT Finer Sarah S Valdes Ana M AM Leslie R David RD Deloukas Panogiotis P Spector Timothy D TD

Genome research 20100310 4

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 th ...[more]

PMID: 20219945

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Dataset Information

Human Aging-associated DNA Hypermethylation Occurs Preferentially at Bivalent Chromatin Domains

Publications

Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains.

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