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

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.

Figure 1

Post-translational modification (PTM) of histones can act to induce (green) or repress (red) the transition of chromatin to an open state. Coupled with the action of histone PTM “readers”, these changes culminate in an increase or repression of the transcription of target genes.