Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development
Figure 2
Establishment and maintenance of imprinted DMRs.
A, A heatmap of mean methylation levels of imprinted DMRs. We classified the 67 known human imprinted DMRs [17], and found that 44 were maternal germline DMRs (M-gDMRs), 2 were paternal germline DMRs (P-gDMRs) and 21 were secondary DMRs (sDMRs). 15 M-gDMRs are reported to be maintained only in the placenta and shown as “Pla-specific gDMRs”. gDMRs other than placenta-specific ones showed 35–65% methylation levels in blood cells but the intermediate methylation levels were not well maintained in ES cells (11/31 showed>75% methylation). Methylation levels are color coded as indicated. The raw data are shown in S1 Table. B, Methylation patterns at the human GNAS locus. The vertical axis indicates the methylation level (%). In this locus, there were two gDMRs and two sDMRs. All DMRs overlap promoter regions. C, Methylation patterns at the human DNMT1 locus. The promoter region of the somatic isoform of DNMT1 (DNMT1s) is known to show maternal allele-specific methylation in the placenta [45]. The DNMT1 DMR was hypomethylated in both ES and blood cells, suggesting placenta-specific protection of the maternal allele from demethylation. D, Box plots of mean methylation levels of gDMRs and oocyte-specific methylated CGIs in blastocysts. Boxes represent lower and upper quartiles and horizontal lines indicate the median. Whiskers extend to the most extreme data points within 1.5 times the interquartile range from the boxes. The open circles indicate the data points outside the whiskers. Methylation levels of mouse gDMRs and oocyte-specific methylated CGIs [5] are shown for comparison. E, Methylation patterns of an oocyte-specific methylated CGI. A single blastocyst was used for the analysis. Black and white circles indicate methylated and unmethylated residues, respectively. The percentages of methylated CpG sites are indicated. F, Bisulfite sequencing analyses of X-linked CGIs hypermethylated in oocytes. A single blastocyst was used for each bisulfite sequencing analysis.