Cell division drives DNA methylation loss in late-replicating domains in primary human cells [methylation array]

ABSTRACT: We present the first experimental evidence that loss of DNA methylation at late-replicating regions, widely documented in aging and cancer, is directly driven by cell division. DNA hypomethylation, particularly at low-density CpGs in A:T-rich, partially methylated domains (PMD solo-WCGWs), tracks cumulative population doublings in primary cell culture. Cell cycle deceleration or full arrest resulted in a proportional decrease in the rate of DNA methylation loss. Lower culture oxygen conditions resulted in a slowed rate of methylation loss, suggesting that these CpGs may also be vulnerable to methylation loss during unscheduled, repair-associated methylation maintenance as well as scheduled, replication-associated methylation maintenance. By studying this methylation context in immortalized primary cells, we identified genomic and epigenomic features that are resistant or more susceptible to methylation loss. Finally, we leveraged this extensive DNA methylation dataset to develop a refined metric for the relative cumulative mitotic histories of human cells. These RNA-sequencing data accompany the larger DNA methylation dataset.

ORGANISM(S): Homo sapiens

PROVIDER: GSE197512 | GEO | 2022/07/25

REPOSITORIES: GEO