Figure 2

Targets and kinetics of CpG island methylation in epiblast cells. (A) Distribution of E8.5 methylation scores in UCSC CGIs located in promoters (-1,000 to 1,000 bp from RefSeq transcription start sites (TSSs)), exons, introns and intergenic sequences. X-linked CGIs are excluded from this analysis. (B) Heatmap showing the methylation in gametes and blastocysts for all the CGIs methylated (>50%) in E8.5 embryos. Approximately half of the CGIs inherit partial methylation from the oocyte. (C) Percentage of CGIs that gain >50% methylation in E8.5 embryos depending on their methylation in blastocysts. CGIs with oocyte-derived methylation in blastocysts have a much higher probability to gain methylation in post-implantation embryos. (D) Kinetics of de novo methylation in CGIs compared with the genome (measured in 400 bp genomic tiles). The graph depicts de novo methylated sequences defined as <20% methylation in E3.5 blastocysts and >50% methylation in E8.5 embryos. (E) Kinetics of de novo methylation for CGIs in TSSs, exons, introns and intergenic sequences (selected as <20% methylation in E3.5 blastocysts and >50% methylation in E8.5 embryos) compared with the whole genome (black line). The lines depict the median methylation at each stage. (F) Examples of single-CpG RRBS profiles at CGIs with delayed DNA methylation in the promoter of Sycp3 and one exon of Blc11b (chr12:107,915,284-107,917,294). Here and in other figures, the green bars depict the position of the CGI. In comparison, the CpG-poor promoter of the Slc6a19 gene gains methylation between E4.5 and E5.5. (G) Gene Ontology terms associated with methylated CGIs (>50% methylation in E8.5 embryos) in TSSs and exons. (H) Distribution of methylation in adult tissues [3] for CGIs with >50% methylation in E8.5 embryos.