KMT2A
KMT2A (lysine methyltransferase 2A, also known as MLL, MLL1, HRX, ALL-1 and TRX1) is a nuclear histone H3 lysine 4 methyltransferase that acts as a transcriptional coactivator. It has an essential role in early development and haematopoiesis. Browse Assay Genie's current range of KMT2A research reagents below, or read on for the biology behind the target.
KMT2A is the catalytic subunit of the MLL1/MLL complex, a multiprotein assembly that mediates methylation of histone H3 at lysine 4 (H3K4me) and acetylation of histone H4 at lysine 16 (H4K16ac). It transfers a methyl group from S-adenosyl-L-methionine to the epsilon-amino group of H3K4 by a non-processive mechanism, predominantly forming H3K4me1 and H3K4me2 marks at active chromatin sites where transcription and DNA repair take place. On its own the enzyme has weak activity and needs other components of the MLL1/MLL complex for full methyltransferase function. It is inactive towards histone H3 phosphorylated on Thr-3, less active towards H3 dimethylated on Arg-8 or Lys-9, and more active towards H3 acetylated on Lys-9. KMT2A also binds unmethylated CpG elements in the promoters of target genes and helps keep them nonmethylated.
The protein is a member of the TRX/MLL subfamily of the histone-lysine methyltransferase family, within the class V-like SAM-binding methyltransferase superfamily. The HGNC groups the KMT2A gene with PHD finger proteins, CXXC-type zinc fingers, bromodomain-containing proteins and SET domain-containing proteins. The SET domain is responsible for H3K4 methyltransferase activity. The KMT2A protein is processed by Taspase 1 into MLL-C and MLL-N fragments, which reassociate and assemble into complexes that regulate specific target genes, including many HOX genes. It is required for transcriptional activation of HOXA9, promotes PPP1R15A-induced apoptosis, and can auto-methylate Cys-3882 when no histone H3 substrate is present.
KMT2A also contributes to circadian control. It is essential for transcription driven by the CLOCK-BMAL1 heterodimer, establishing a permissive chromatin state through rhythmic H3K4 methylation that directs circadian acetylation at H3K9 and H3K14 and allows CLOCK-BMAL1 recruitment. The gene was originally named for its role in myeloid/lymphoid or mixed-lineage leukaemia, as a trithorax homologue. Multiple chromosomal translocations involving it cause certain acute lymphoid and acute myeloid leukaemias.
KMT2A deposits H3K4me1 and H3K4me2 marks at active chromatin, making it a central enzyme for studying epigenetic transcriptional activation.
Chromosomal translocations involving KMT2A cause certain acute lymphoid and acute myeloid leukaemias, so it is a key gene in leukaemia biology.
KMT2A is essential in early development and haematopoiesis, and is required for activation of target genes such as HOXA9.
KMT2A mediates rhythmic H3K4 methylation that enables CLOCK-BMAL1 recruitment, linking histone modification to circadian transcription.
KMT2A is the catalytic subunit of the MLL1/MLL complex and methylates histone H3 at lysine 4, a mark linked to active transcription. It regulates target genes including HOX genes, and supports circadian gene expression through CLOCK-BMAL1. It needs other complex components for full activity.
The gene was first identified through leukaemia translocations, giving names such as MLL, MLL1, ALL-1 and HRX. Others, including TRX1 and Trithorax-like protein, reflect its homology to Drosophila trithorax. CXXC7 refers to its CXXC-type zinc finger. HGNC now uses KMT2A.
Multiple chromosomal translocations involving KMT2A cause certain acute lymphoid and acute myeloid leukaemias. The mouse ortholog is Kmt2a. The protein is processed by Taspase 1 into MLL-N and MLL-C fragments; check the datasheet of any product for its validated reactivity.
Other histone lysine methyltransferases and epigenetic regulators with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q03164; product specifications from Assay Genie datasheets.