GSE53610
Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells [human]
Stable maintenance of gene regulatory programs is essential for normal function in multi-cellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type specific gene expression. Here we use new methods to study distributions of DNA methylation patterns within cell populations to show that embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells. Quantitative tuning of this equilibrium leads to convergence into a binary epigenetic configuration maintaining a sharp distinction between methylated and unmethylated regions. In contrast, somatic cells transmit considerable epigenetic information from mother to daughter cell. Paradoxically, the persistence of the somatic epigenome makes it more vulnerable to noise, since random epi-mutations can be preserved and accumulate to massively perturb the binary epigenomic ground state. Epigenetic perturbation is not observed in the pluripotent state, since the rapid turnover-based equilibrium continuously reinforces the canonical state. This dynamic epigenetic equilibrium also explains how the somatic epigenome can be reprogrammed quickly and accurately following induced pluripotency. Overall design: Comparison of single cell clonal population DNA methylation variation to the original population in 6 cell lines and 1 primary