Types of histone modification

Chromatin architecture, nucleosomal positioning, and ultimately access to DNA for gene transcription, is largely controlled by histone proteins. Each nucleosome is made of two identical subunits, each of which contains four histones: H2A, H2B, H3, and H4. Meanwhile, the H1 protein acts as the linker histone to stabilize internucleosomal DNA and does not form part of the nucleosome itself.

Histone proteins undergo post-translational modification (PTM) in different ways, which impacts their interactions with DNA. Some modifications disrupt histone-DNA interactions, causing nucleosomes to unwind. In this open chromatin conformation, called euchromatin, DNA is accessible to binding of transcriptional machinery and subsequent gene activation. In contrast, modifications that strengthen histone-DNA interactions create a tightly packed chromatin structure called heterochromatin. In this compact form, transcriptional machinery cannot access DNA, resulting in gene silencing. In this way, modification of histones by chromatin remodeling complexes changes chromatin architecture and gene activation.

At least nine different types of histone modifications have been discovered. Acetylation, methylation, phosphorylation, and ubiquitylation are the most well-understood, while GlcNAcylation, citrullination, crotonylation, sumoylation, and isomerization are more recent discoveries that have yet to be thoroughly investigated. Each of these modifications are added or removed from histone amino acid residues by a specific set of enzymes.

Together, these histone modifications make up what is known as the histone code, which dictates the transcriptional state of the local genomic region. Examining histone modifications at a particular region, or across the genome, can reveal gene activation states, locations of promoters, enhancers, and other gene regulatory elements.

The most common histone modifications. To find out more, see our full histone modifications poster.