Chromatin Remodeling in Heart Failure

Abstract

Chromatin provides a dynamic DNA scaffold that reacts to physiological and pathological signals to control the accessibility of DNA sequence and the genomic responses to environmental stimuli. Chromatin can be regulated by nucleosome remodeling, histone modification, and DNA methylation. Histone and DNA modifications occur by covalent alterations of the side chains of histone or bases of DNA, catalyzed by specific histone- and DNA-modifying enzymes, whereas nucleosome or chromatin-remodeling controls noncovalent changes of nucleosomes, including their position and histone composition, effected by adenosine triphosphate (ATP)-dependent chromatin-remodeling complexes. Within the nucleosome, the chromatin remodelers can replace canonical histones with variant forms of histones, which are involved in cardiac stress response. In addition, chromatin remodelers can interact with histone- and DNA-modifying enzymes to control chromatin structure and reprogram gene expression in pathologically stressed hearts. More recently, a chromatin-remodeling factor was found to interact with a cardiac-specific long noncoding RNA to control gene expression and maintain cardiac homeostasis. These functional aspects of chromatin remodelers are critical for the pathogenesis of cardiomyopathy and heart failure. This chapter is focused on the recent progress in understanding the roles of chromatin-remodeling factors in heart failure, new chromatin-based mechanisms, and potential therapeutic strategies for heart failure.