Readers, writers, and erasers: chromatin as the whiteboard of heart disease

Circ Res. 2015 Mar 27;116(7):1245-53. doi: 10.1161/CIRCRESAHA.116.303630.

Abstract

Dynamic packaging of DNA into strings of nucleosomes is a major mechanism whereby eukaryotic cells regulate gene expression. Intricate control of nucleosomal structure and assembly governs access of RNA polymerase II to DNA and consequent RNA synthesis. As part of this, post-translational modifications of histone proteins are central to the regulation of chromatin structure, playing vital roles in regulating the activation and repression of gene transcription. In the heart, dynamic homeostasis of histone modification-driven by the actions of modifiers and recruitment of downstream effectors-is a fundamental regulator of the transcriptional reprogramming that occurs in the setting of disease-related stress. Here, we examine the growing evidence for histone modification as a key mechanism governing pathological growth and remodeling of the myocardium.

Keywords: chromatin; chromatin assembly and disassembly; epigenomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Animals
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism
  • Cardiotonic Agents / therapeutic use
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Chromatin / ultrastructure
  • Chromatin Assembly and Disassembly
  • Epigenesis, Genetic
  • Fetal Heart / growth & development
  • Gene Expression Regulation*
  • Heart / embryology
  • Heart Diseases / genetics*
  • Histone Acetyltransferases / physiology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histone Deacetylases / physiology
  • Histone Deacetylases / therapeutic use
  • Histone Demethylases / physiology
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / physiology
  • Histones / physiology*
  • Humans
  • Methylation
  • Multiprotein Complexes
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / metabolism
  • Myocardium / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / ultrastructure
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • Rats
  • Transcription, Genetic

Substances

  • Cardiotonic Agents
  • Chromatin
  • Histone Deacetylase Inhibitors
  • Histones
  • Multiprotein Complexes
  • Nucleosomes
  • Histone Demethylases
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Histone Acetyltransferases
  • Histone Deacetylases