Histones primary functions are compact DNA strands and impact chromatin regulation. Chromatin is a combination of DNA and protein which makes up the contents of a cell nucleus. Without histones, the unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 millimeters of chromatin, which, when duplicated and condensed during mitosis, result in about 120 micrometers of chromosomes. Because DNA wraps around histones, they also play a important role in chromatin regulation and in the regulation of gene expression. A histone modification is a covalent post-translational modification (PTM) to histone proteins which includes methylation, phosphorylation, acetylation, ubiquitylation, and SUMOylation. Methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Phosphorylation is the addition of a phosphate group to a molecule.

Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound. The addition of ubiquitin to a substrate protein is called ubiquitination or ubiquitylation. SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle. The PTMs made to histones can impact gene expression by altering chromatin structure or recruiting histone modifiers. Histone proteins act to package DNA, which wraps around the eight histones, into chromosomes. Histone modifications act in diverse biological processes such as transcriptional activation/inactivation, chromosome packaging, and DNA damage/repair.