Extended Data Fig. 4: cDKO-DMRs overlap with tissue-specific enhancers.

a, TET1 enrichment (from ref. ²¹) for LINE 5’UTRs and active H1 enhancers. b, A region within the gene NCOR2 that has many cDKO-DMRs. These lose methylation in different somatic tissues as shown below. H3K27ac and H3K4me1 tracks display ENCODE data derived from H1 ESCs. Methylation tracks are from ref. ⁶. c, The percentage of overlap with putative somatic enhancers (defined in ref. ³²) for class 1 and class 2 cDKO-DMRs, an equal number of same-sized randomly selected regions, H3K4me1 peaks in ESCs (H1) and 1 kb tiles with matched CpG density to cDKO-DMRs (3.1–3.3%). d, B cell enhancers (defined in ref. ³²) separated by methylation levels in WT ESCs, DKO ESCs and B cells. e, Composites showing methylation levels in passage (P) 3 and 28 DKO ESCs for P3 and P28 DKO-DMRs. f, For 86 different previously defined putative enhancer sets³², the stacked bar plots display the proportion that are already hypomethylated in WT ESCs, lose methylation in DKO cells (WT – DKO difference > 0.2) or remain methylated in DKO cells. For this analysis, P28 DKO was used. g, Schematic of in vitro pancreatic islet cell differentiation (from ref. ³³). h, The proportion of cDKO-DMRs or P28 DKO-DMRs that overlap with each set of cell type specific enhancers. Enhancers were previously defined³³. i, For regions defined as showing dynamic methylation changes during differentiation to beta islet cells³³, methylation levels are shown for these cell types as well as HUES64 WT and DKO-A ESCs.