DNA Methylation Reprograms Cardiac Metabolic Gene Expression in End-Stage Human Heart Failure.

DNA Methylation Reprograms Cardiac Metabolic Gene Expression in End-Stage Human Heart Failure. Am J Physiol Heart Circ Physiol. 2019 Jul 12;: Authors: Pepin ME, Drakos S, Ha CM, Tristani-Firouzi M, Selzman CH, Fang JC, Wende AR, Wever-Pinzon O Abstract Heart Failure (HF) is a leading cause of morbidity and mortality in the United States and worldwide. As a multifactorial syndrome with unpredictable clinical outcomes, identifying the common molecular underpinnings that drive HF pathogenesis remains a major focus of investigation. Disruption of cardiac gene expression has been shown to mediate a common final cascade of pathological hallmarks, wherein the heart reactivates numerous developmental pathways. Although the central regulatory mechanisms that drive this cardiac transcriptional reprogramming remain unknown, epigenetic contributions are likely. In the current study we examined whether the epigenome, specifically DNA methylation, is reprogrammed in HF to potentiate a pathological shift in cardiac gene expression. To accomplish this, we used paired-end whole-genome bisulfite sequencing and next-generation RNA sequencing of left ventricle tissue obtained from 7 patients with end-stage HF and 3 non-failing donor hearts. We found that differential methylation was localized to promoter-associated CpG islands, which are established regulatory regions of downstream genes. Hyper-methylated promoters were associated with genes involved in...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research