for the mC in the CHH sequence context. Lastly, mCHG and mCHH DMRs overlapping or closer than 100 kb were joined and the final set of regions was checked for having mCHG+mCHH fold enrichment of at least 2-fold between H1 and ADS-iPSCs. This set of 78 DMRs hypomethylated in ADS-iPSCs (Supplementary Fig. 15c–f) was further refined, considering the size and overlap with repressive histone marks. The final set of 22 regions reported in Fig. 5 includes all the DMRs larger than 1 Mb (17) and a range of smaller ones. Also, the 22 final non-CG mega-DMRs encompass ∼92% of the initial set of 78 DMRs, based on size in bp.
