Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC)  5-mCs oxidation product  is unknown in the context of the heart. Here, we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks gene bodies of highly expressed genes and distal regulatory regions with enhanced activity. Pathological hypertrophy is characterized by a partial shift towards a fetal-like distribution pattern.;	We further demonstrate a regulatory function of TET2 and provide evidence that the expression of key cardiac genes, such as Myh7 is modulated by TET2-mediated 5-hmC deposition on the gene body and at enhancers in cardiac cells.;	We thus provide the first genome-wide analysis of 5-hmC in the cardiomyocyte, and establish the role of this epigenetic modification in heart development and disease SOURCE: Paolo Kunderfranco (Paolo.Kunderfranco@humanitasresearch.it) - Cardiovascular Research Humanitas Clinical and Research Center

Pluto Bioinformatics

GSE79883: Gene expression profiling during cardiac maturation, hypertrophy and after KD of TET2