Post-translational modifications

Eukaryotic genomes are highly organized into transcriptionally active (euchromatic) and silent (heterochromatic) chromatin regions. Conversion of chromatin between the two major forms is regulated in part through interactions between chromatin-modifying enzymes and nucleosomes. Nucleosomes are the fundamental unit of chromatin and consist of approximately 147 base pairs of DNA wrapped around an octameric core of the histones H₂A, H₂B, H₃, and H₄ [1]. Chromatin structure plays a key role in the regulation of gene activity and its mis-regulation is a theme characteristic of many types of disease and cancer [1]. The N-terminal tails of histones, which protrude outside of the nucleosome core [2], are subject to many sites and types of post-translational modifications (PTMs), which, in turn, help regulate biological processes through altering nucleosome stability or the function of chromatin-associated complexes [3, 4]. For example, acetylation of histone lysine residues on the N-terminal tail has been correlated to active gene transcription either by countering the negative charge of the DNA backbone, or through the recruitment or stabilization of bromodomain-containing proteins [3, 5, 6].