Although non-CG DNA methylation levels and distribution were very similar between ES cells and iPSCs on a whole-genome and chromosomal scale (Fig. 1), a systematic comparison of non-CG methylation levels between the H1 and the ADS-iPSC lines throughout the autosomes revealed the presence of 29 large, non-CG differentially methylated regions (FDR = 1%; Supplementary Table 4). These non-CG ‘mega’-DMRs tended to be very large, with half greater than 1 Mb in length, the longest ∼4.8 Mb, and in total all 29 made up 32.4 Mb (Fig. 5a, inset). The majority of non-CG mega-DMRs were hypomethylated in the mCH context in the ADS-iPSC line (22 of 29, total length = 29.1 Mb; Supplementary Fig. 15a, b). The H1 hypomethylated non-CG mega-DMRs contained 36 genes enriched for biological processes related to epidermal cell differentiation (54% of 36 genes; P value =1.5 × 10−35), and that predominantly were not expressed in H1 cells but were transcribed at a low level in ADS-iPSCs (Supplementary Table 5). Focusing subsequent analysis on the 22 non-CG mega-DMRs hypomethylated in the ADS-iPSC line compared to the H1 line,