Histone lysine methyltransferase (HKMT)

Histone lysine methyltransferases (HKMTs) are a diverse group of enzymes responsible for the site-specific methylation of lysine residues on histone proteins, most notably histones H3 and H4. These enzymes utilize S-adenosyl-L-methionine (SAM) as a methyl donor to add one, two, or three methyl groups, which serves as a key epigenetic mechanism for regulating gene expression and chromatin architecture (Source: UniProt, PubMed). HKMTs are broadly categorized into SET domain-containing proteins and non-SET domain proteins like DOT1L. Aberrant activity or expression of various HKMTs is strongly associated with oncogenesis, where they can silence tumor suppressor genes or activate oncogenic pathways (Source: NIH, Nature Reviews Drug Discovery). Consequently, they have emerged as high-priority therapeutic targets, leading to the development of inhibitors such as tazemetostat, which targets EZH2 in epithelioid sarcoma and follicular lymphoma. Therapeutic challenges include achieving isoform selectivity and managing the systemic effects of altering fundamental epigenetic processes (Source: PubMed, ClinicalTrials.gov).

Other names

Multiple histone lysine methyltransferasesLysine N-methyltransferaseKMTProtein-lysine N-methyltransferaseHistone methyltransferase

Inhibition of the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to specific lysine residues on histone tails, thereby modulating chromatin state and gene transcription.