Chromatin Remodeling in Heart Failure
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.
KeywordsChromatin Remodeler Histone Variant ATPase Subunit Heart Failure Therapy Repressive Chromatin
Compliance with Ethical Standards
C.P.C. is the Charles Fisch Scholar of Cardiology and was supported by National Institutes of Health (NIH; HL118087, HL121197, HL085345), the American Heart Association (National Scientist Development Award, Established Investigator Award 12EIA8960018), Oak Foundation, Baxter Foundation, Lucile Packard Heart Center Research Program, California Institute of Regenerative Medicine New Faculty Award, Children’s Heart Foundation, the CHARGE Syndrome Foundation, March of Dimes Foundation (#6-FY11-260), Indiana University (IU) School of Medicine—IU Health Strategic Research Initiative, and the IU Physician-Scientist Initiative, endowed by Lilly Endowment.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Olson EN, Backs J, McKinsey TA (2006) Control of cardiac hypertrophy and heart failure by histone acetylation/deacetylation. Novartis Found Symp 274: 3–12; discussion 13–19, 152–155, 272–156Google Scholar