Epigenetics and Chromatin Remodeling in Adult Cardiomyopathy

Abstract

The manipulation of chromatin structure regulates gene expression and the flow of genetic information. Histone modifications and ATP-dependent chromatin remodeling together with DNA methylation are dynamic processes that modify chromatin architecture and profoundly modulate gene expression. Their coordinated control is key to ensuring proper cell commitment and organ development, as well as adaption to environmental cues. Recent studies indicate that abnormal epigenetic status of the genome, in concert with alteration of transcriptional networks, contribute to the development of adult cardiomyopathy such as pathological cardiac hypertrophy. Here we consider the emerging role of different classes of chromatin regulators and how their dysregulation in the adult heart alters specific gene programs with subsequent development of major cardiomyopathies. Understanding the functional significance of the different epigenetic marks as points of genetic control may represent a promising future therapeutic tool.

Identification of a regulatory domain controlling the Nppa-Nppb gene cluster during heart development and stress

“…Such modifications have been associated with the development of cardiomyopathies in the adult heart (Mahmoud and Poizat, 2013). Demethylation of H3K9 at the promoter regions of NPPA and NPPB was associated with activation of their expression in failing human left ventricular myocardium, whereas H3K9ac was not changed and H3K27ac was modestly increased (Hohl et al, 2013), in accordance with our observations (Fig.…”

The histone demethylase PHF8 represses cardiac hypertrophy upon pressure overload

“…Histone acetylation, methylation, phosphorylation, ribosylation, DNA methylation and ATPdependent chromatin remodelers have been reported to participate in cardiac hypertrophy and failure [4]. For instance, histone H3K4me2/3, H3K9me3, H3K27me3, H3K26me3, H3K36me3 and H3K79me have been reported to control the expression of cardiac fetal genes and modulate cardiac hypertrophy, angiogenesis and dilation as well as subsequent heart failure [5][6][7][8].…”

Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy

“…Based on recent findings, now it is well understood that genetic predisposition alone is insufficient to explain the complexity of the disease entirely, hence this urge a necessity to emphasize on epigenetic mechanisms involved in the development of diabetic complications (Keating & El Osta, 2013). Epigenetics can be defined as the heritable changes in gene expression patterns without any alteration in the underlying DNA sequences; this includes DNA methylation, post translational histone modifications (PTHMs) and, micro-RNA regulation of mRNA translation (Asrih & Steffens, 2013;Keating & El Osta, 2013;Mahmoud & Poizat, 2013). Among the above mentioned epigenetic changes, the current study focuses on post translational histone modifications (PTHMs) in diabetic cardiomyopathy (DCM).…”