Role of DNA methylation and hydroxy methylation in the progression of Diabetic cardiomyopathy.

Diabetic Cardiomyopathy (DCM), one of the most debilitating complications of diabetes is a major cause of morbidity and mortality in diabetic patients. However, the underlying mechanisms involved in the pathogenesis of DCM are still incompletely understood. Increasing evidence shows that hyperglycemia can regulate gene expression by epigenetic modifications, such as DNA methylation, which can persistently exist even after glucose normalization. There is very scant information on the epigenetic regulation of the genes involved in the pathophysiology of DCM. Here, we sought to decipher global differential methylation and hydroxymethylation patterns in the heart tissue of the streptozotocin (STZ) induced diabetic rat model. We did Genome-wide methylation/hydroxymethylation analysis by MeDIP-seq and hMeDIP-seq respectively. There was increased enrichment of 5mC and hmC in the genomic DNA of diabetic heart tissue. Most of these hypermethylation marks were seen in the gene body rather than CpG island or promoter regions. Most enriched genes found in diabetic cardiac tissue were related to metabolic pathways, and signaling pathways like MAPK, calcium signaling, and cardiac homeostasis. Further validation of this genomic data at a gene-specific level by qPCR and bisulfite sequencing can help us to understand the effect of differential methylation in different regions of the genome on gene expression. This study can have critical implications for early prevention and provide unique opportunities to develop novel therapeutic approaches.