KMT2

KMT2, or lysine methyltransferase 2, refers to a family of histone lysine methyltransferases that catalyze the methylation of histone H3 on lysine 4 (H3K4). Through this activity, KMT2 enzymes help establish and maintain transcriptionally active chromatin at gene promoters and regulatory elements, contributing to gene expression programs during development and differentiation.

Most KMT2 family members function as part of COMPASS-like multi-subunit complexes. They typically contain a SET domain responsible for catalytic activity near the C-terminus and various targeting domains that interface with core subunits such as WDR5, RbBP5, ASH2L, and DPY30. In some members, the catalytic activity may be reduced or regulated, and the proteins can have non-catalytic regulatory roles.

Key human genes in the family include KMT2A, KMT2B, KMT2C, and KMT2D, with additional paralogs such as KMT2F and others described in some species. These enzymes are widely expressed and can have tissue- and context-specific functions.

Functionally, KMT2 enzymes contribute to activation of gene transcription by establishing H3K4 methyl marks at promoters and enhancers, influencing processes from embryonic development and stem cell identity to hematopoiesis and neural development.

Mutations and chromosomal rearrangements involving KMT2 genes are linked to disease. MLL (KMT2A) rearrangements are frequent in pediatric leukemias. Germline mutations in KMT2D cause Kabuki syndrome, while KMT2A mutations are associated with Wiedemann-Steiner syndrome; other alterations in KMT2 genes are implicated in developmental disorders and cancer in various contexts.