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Senescent cells harbour features of the cancer epigenome.

ABSTRACT: Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, late-replicating, lamin-associated domains and is linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence. Low-level gains of methylation are enriched in CpG islands, including at genes whose methylation and silencing is thought to promote cancer. Gains and losses of methylation in replicative senescence are thus qualitatively similar to those in cancer, and this 'reprogrammed' methylation landscape is largely retained when cells bypass senescence. Consequently, the DNA methylome of senescent cells might promote malignancy, if these cells escape the proliferative barrier.

SUBMITTER: Cruickshanks HA

PROVIDER: S-EPMC4106249 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Senescent cells harbour features of the cancer epigenome.

Cruickshanks Hazel A HA McBryan Tony T Nelson David M DM Vanderkraats Nathan D ND Shah Parisha P PP van Tuyn John J Singh Rai Taranjit T Brock Claire C Donahue Greg G Dunican Donncha S DS Drotar Mark E ME Meehan Richard R RR Edwards John R JR Berger Shelley L SL Adams Peter D PD

Nature cell biology 20131124 12

Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, late ...[more]

PMID: 24270890

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Senescent cells harbour features of the cancer epigenome.

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Senescent cells harbour features of the cancer epigenome.

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