A bimodal gene body methylation pattern associated with transcription in human oocytes.

<p><b>A,</b> A density scatterplot of gene body methylation levels and transcription levels <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004868#pgen.1004868-Yan1" target="_blank">[43]</a> in human oocytes. The data of mouse oocytes <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004868#pgen.1004868-Kobayashi1" target="_blank">[5]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004868#pgen.1004868-Shirane1" target="_blank">[11]</a> are also shown for comparison. Only genes longer than 5 kb were analyzed. For genes with RPKM less than 0.01, RPKM was set as 0.01. The density is color-coded as indicated. <b>B,</b> Mean methylation levels within 5 kb of transcription start sites (TSS) in human oocytes. Genes (>5 kb) were classified into two groups (log₂(RPKM)>−5 and ≤−5). Methylation levels were smoothed using 5 bp non-overlapping sliding windows. <b>C,</b> Conservation of gene body methylation levels between human and mouse oocytes. 783 and 188 genes showed human-specific and mouse-specific gene body hypermethylation, respectively. 5076 and 1151 genes were hypermethylated and hypomethylated in both types of oocytes, respectively. The raw data are shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004868#pgen.1004868.s006" target="_blank">S2 Table</a>. <b>D,</b> GO analysis of 783 genes with human-specific gene body hypermethylation. The top three GO terms (biological process and molecular function) are indicated with gene counts, the proportion (%) and BH-corrected <i>P</i>-values. No GO term was enriched in genes with mouse-specific gene body hypermethylation. <b>E,</b> Gene body methylation levels and transcription levels of DNA methylation regulators in human and mouse oocytes. <i>DNMT3L</i> and <i>ZFP57</i> showed gene body hypomethylation and were not expressed (RPKM<0.01) in human oocytes. <i>DNMT3B</i> (RPKM = 76.0) showed 10-fold higher expression than <i>DNMT3A</i> (RPKM = 7.6) in human oocytes. In contrast, <i>Dnmt3b</i> (RPKM = 4.9) showed ∼6-fold lower expression than <i>Dnmt3a</i> (RPKM = 30.6) in mouse oocytes. <b>F,</b> Methylation patterns at human <i>DNMT3L</i> and <i>ZFP57</i> loci and mouse <i>Dnmt3l</i> and <i>Zfp57</i> loci. The vertical line indicates the methylation level (%) and the baseline is set at 50% to highlight unmethylated CpGs. CpGs with>50% and <50% methylation are shown in red and grey, respectively.