DNA methylation oscillations at CpG poor enhancers in primed embryonic stem cells [amplicon-Seq]

Mouse embryonic stem cells (ESCs) primed for differentiation display dynamic heterogeneity characterised by stochastic switching between transcriptional states, and recent advances have highlighted the heterogeneous and dynamic nature of DNA methylation in these. Using single cell sequencing we report global oscillations in ESC DNA methylation that affect particularly CpG poor regions including distal enhancers. These oscillations are dependent on DNA methylation turnover by Dnmt3 and Tet enzymes and influence the probability of transcriptional state switching. Our observations suggest that regulated DNA methylation heterogeneity may contribute to lineage priming in cells poised for differentiation. 2i ES cells transferred into serum media and collected at 48 time points. Control cells were 2i ES cells collected at the same time points (i.e. without changing to serum media)