All ATAC-seq or 5mC-seq data are plotted over the naive-specific set defined in 5iLAF (5032 peaks), a subset that contained an AP2 motif but no KLF motif (1054 peaks), a subset that contained a KLF motif but no AP2 motif (1551 peaks) and primed-specific peaks (2562 peaks). a, Blastocyst ATAC-seq reads are strongly enriched over naive-specific ATAC-seq peaks, including the AP2+KLF- and KLF+AP2- motif subsets, but are less enriched over primed-specific peaks. b, DNA methylation from primed and naive cells plotted over different ATAC-seq peak sets. Note that cells cultured in t2iLGö show drops in methylation over all naive-specific peak sets, including the AP2+ peak set, indicating that this same regions are likely to be open chromatin in the t2iLGö conditions. c, DNA methylation from oocyte and blastocyst are plotted relative to ATAC-seq peak sets. Note sharp loss of DNA methylation in blastocyst over the naive-specific sets. d, After fertilization, the paternal genome is demethylated while the maternal genome remains methylated, so thoughout the blastocyst genome the DNA methylation level is very close to half the Oocyte methylation level12. Thus, we plotted (methylation in blastocyst – 50% methylation level in oocyte) to determine regions that have undergone localized demethylation during embryogenesis. Sharp demethylation is observed over naive-specific peak sets, validating their identity as enhancers.