Histonmethylation

Histone methylation is a post-translational modification in which methyl groups are added to lysine or arginine residues on histone proteins by histone methyltransferases. This modification can influence chromatin structure and gene expression, and the installed marks may be stable or dynamically regulated by cellular signals.

Molecular players include histone methyltransferases that install methyl groups on lysines (primarily SET-domain containing KMTs and DOT1L) and arginine methyltransferases (PRMTs). Lysine methylation can occur as mono-, di-, or tri-methylation, while arginine methylation yields symmetric or asymmetric dimethylation. Demethylases, such as LSD1/KDM1 and JmjC-domain-containing enzymes (KDMs), remove methyl groups from histones. The repertoire of methyl marks and their readers—proteins with domains such as chromodomains, Tudor, or MBT that recognize specific methylation states—translates the chemical signal into downstream regulatory outcomes.

Key histone marks include H3K4me3 and H3K4me1 associated with active promoters and enhancers, H3K27me3 and H3K9me3 linked to transcriptional repression and heterochromatin, H3K36me3 with transcriptional elongation, and H4K20me3 also related to compact chromatin. The functional outcome of a given methyl mark depends on the residue, its methylation state, and the local chromatin context.

Biological roles are broad, encompassing development, genomic imprinting, X-chromosome inactivation, and DNA damage repair. Dysregulation of histone methylation is implicated in various cancers and developmental disorders. Epigenetic therapies target these enzymes, with inhibitors against EZH2 or DOT1L illustrating the clinical relevance of histone methylation regulation. Detection and study commonly employ chromatin immunoprecipitation (ChIP-seq), CUT&RUN, and mass spectrometry.