Chromatin as the Whiteboard of Heart Disease

Eukaryotic DNA is packaged, protected, and regulated by a histone protein core, around which the DNA is wrapped. This structure, termed chromatin, can be condensed and “closed,” a state associated with relative transcriptional repression. Conversely, chromatin can be “open,” a state which allows proteins governing transcription to access the DNA and effect RNA synthesis. Regulation of chromatin in its various active states is controlled significantly through post-translational modifications (PTMs) of the core histone proteins. Primarily targeting amino acids within the N-terminal tails of these proteins, a wide range of PTMs occur, including phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, and GlcNAcylation. Regulation of chromatin by reversible incorporation of phosphate, acetyl groups, or methyl groups within histone tails is best understood. Governance of chromatin structure through histone PTMs has emerged as a key driver of transcriptional responses in numerous cells. Likewise, histone writers, erasers, and readers— the protein machinery that adds, removes, or recognizes these PTMs—have become central figures in our understanding of physiological responses in many cell types (Figure). Writers, enzymes that add PTMs to histones, are divided into classes on the basis of the specific PTM they effect. Similarly, erasers, enzymes that remove specific PTMs from histone substrates, are divided into PTM-specific classes. Review