Fig. 5. A group of promoters targeted by PRC2 exhibits H3K4me3 hypermethylation and DNA hypomethylation in PAs.

A Hierarchical clustering of samples based on the presence of H3K4me3 at the promoters. Color scale and numbers on the heatmap indicate a similarity between H3K4me3 patterns at the promoters (dark blue, 1 - identical; white, 0 - maximally dissimilar). Red box – the identified cluster of PA samples. B Expression of transcripts associated with promoters exhibiting H3K4me3 hypermethylation in PAs. The p value was calculated with one-sided Mann–Whitney U test. C Enrichment of binding sites from the ENCODE transcription factor ChIP-seq data in PAs specific promoters compared to promoters active in all samples. The number of peaks for each DNA-binding protein is given in parentheses; enrichment values per megabase are shown next to each bar and indicated with proportional coloring (red – highest, blue-lowest). D DNA methylation in promoters exhibiting H3K4me3 hypermethylation in PAs and having an EZH2 binding site. Methylation levels were determined with WGBS. Samples with IDH mutations were excluded from the plot. Colors indicate sample grades (light orange – PA, dark orange – DA, red – GB/PG). E DNA methylation in promoters exhibiting H3K4me3 hypermethylation in PAs and having an EZH2 binding site in an independent cohort, determined by HumanMethylation450 BeadChip array. Colors indicate sample grades (light orange – PA, red – GB). F GO terms enriched in the set of the PA-specific genes with EZH2 binding sites in promoters. The enrichment was calculated using the PANTHER Overrepresentation Test . More detailed results are provided in Supplementary Fig. 5E. In panels (B), (D), and (E) data are represented as boxplots in which the box shows the quartiles of the dataset, the middle line is the median and the whiskers extends to the largest or smallest value no further than 1.5× the inter-quartile range.