The eukaryotic genome is regulated by a variety of epigenetic mechanisms that establish and maintain proper gene expression profiles to control cell identity and fate. One of these vital mechanisms is accomplished by chromatin, which is the packaging medium for genomic DNA. The chromatin polymer consists of individual nucleosomes in which the DNA is wrapped around an octamer of the canonical histone proteins H2A, H2B, H3, and H4. The histone proteins are highly post-translationally modified, and these modifications (PTMs) have an impact on the local chromatin environment through both direct biophysical perturbations and recruitment of downstream effectors. Different PTM chemotypes (e.g., methylation, acetylation, ADP-ribosylation) at different sites within the histones act as dynamic signals to delineate specific chromatin states. Thus, far from being a passive scaffold for the genome, chromatin actively controls access to the underlying genetic material to aid in regulating transcription, translation, and repair. Importantly, when histone PTMs and other epigenetic factors are disrupted, these processes are misregulated leading to diseases such as cancer and developmental disorders.
