Fig. 7
Dynamics of mCpG and histone modifications in gene bodies and enhancer regions of cardiac myocyte genes during heart development and in chronic heart failure. During cardiac myocyte development, mCpG of enhancers (LMR low methylated region, Fig. 4) and genic regions (gUMR genic unmethylated region, Fig. 2) and canonical histone marks cooperate to induce (MYH6, RYR2, TNNI3) or repress (MYL4, NPPA, TNNI1) cardiac myocyte genes (left panel, Fig. 1f). In failing cardiac myocytes (right panel), induction of disease-associated genes is accompanied by active histone marks without changes in gene body mCpG (Fig. 3b). Some LMRs showed small changes in mCpG in heart failure (Fig. 5a). Low methylated regions with enhancer signature were significantly enriched for single-nucleotide polymorphisms (SNP), which have been linked with cardiac disease (Fig. 6)
