Title: Sub-cell cycle kinetics in DNA methylation reveal shared molecular origins of regulatory variation and age-related drift
Abstract: DNA methylation is a heritable epigenetic modification that plays an essential role in development, cancer and aging. Recent experiment identified pronounced genome-wide delay in post-replication DNA methylation maintenance in ESCs. The delay shows site-to-site heterogeneity across genome, but its functional indication is still unclear. Here, by gene ontology analysis, we found the CpGs with pronounced delay in post-replication methylation and intermediate methylation(IM) level associated with cell fate especially at the distal region (> 5kb to TSS). Moreover, through enrichment analysis, we uncovered these specific CpGs are enriched in enhancer, promoter and cell fate related TF binding regions, such as NANOG, OCT4 binding regions. By linking the post-replication delay with aging data, we also found the sub-cell cycle kinetics in DNA methylation is associated with epigenetic drift.