We also studied DNA methylation changes in three different systems. First, we studied DNA methylation changes during Embryonic Stem Cell (ESC) differentiation49-50. We identified regions that lost methylation (Differentially Methylated Regions, DMRs, Table S4c) upon differentiation of ESCs (E003) to mesodermal (E013), endodermal (E011), and ectodermal (E012) lineages (Fig. 4h). Each lineage showed a largely distinct set of ~2200-4400 DMRs, that are enriched for distinct transcription factor binding events (Fig. 4h, right column)51, consistent with their distinct developmental regulation. Upon further differentiation, ectodermal DMRs remained hypomethylated in three neural progenitor populations 52, despite the usage of distinct hESC lines, and mesodermal and endodermal DMRs remained highly methylated (Fig. 4h), highlighting the lineage-specific nature of changes in DNA methylation during early differentiation49,53.
