Fig. 2
Genic CpG demethylation of cardiac myocyte genes. a Genes were grouped according to their mean expression level (FPKM) in adult non-failing cardiac myocyte nuclei. Numbers of genes in each expression group are listed in the table. Average plots for mCpG and levels of H3K4me3, H3K4me1, H3K36me3, H3K27ac, and H3K27me3 are represented from TSS (transcription start site) to TES (transcription end site) including 10 kb flanking regions for each group. b Characterization of genes with pronounced genic demethylation. Criteria for these genes were gUMR length ≥5 kb and/or gUMR overlapping with ≥25% of a gene. Heatmaps of mean gUMR mCpG, enrichment of genic H3K27ac and H3K27me3, and gene expression. Genes were clustered into two groups according to developmental alteration of mCpG and presence of H3K27me3. Gene ontology analysis of groups I and II shows most highly enriched GO terms, representative genes, and Bonferroni corrected p-values. c Analysis of genes with gUMR-DMRs between fetal and adult non-failing cardiac moycytes. d Gene ontology analysis of genes with differential gUMR methylation between fetal and adult non-failing cardiac myocytes. The list shows most highly enriched GO terms, representative genes, and Bonferroni corrected p-values. Gene expression of genes with hypomethylated (upper graph) or hypermethylated gUMRs (lower graph) in adult non-failing vs. fetal cardiomyocytes is displayed as violin plots with inserted box and whisker plots. ***p < 0.001 by ANOVA. e Changes in active histone marks (upper graphs), mCpG, 5hmC levels and H3K27me3 (lower graphs) in hypomethylated (A, group 1) or hypermethylated (A, group 2) gene bodies in adult non-failing vs. fetal cardiac myocytes. Figures show data from n biological replicates: mCpG, n = 3–5; H3K27ac, H3K9ac, H3K36me3, H3K4me1, H3K4me3 and H3K27me3, n = 3; RNA, n = 3–4
