Histone-lysine N-methyltransferase 2B (KMT2B)

Histone-lysine N-methyltransferase 2B (KMT2B) is a large, multidomain enzyme responsible for catalyzing the trimethylation of histone H3 at lysine 4 (H3K4), a key epigenetic mark linked to transcriptional activation[1][2][3]. KMT2B is part of the KMT2/MLL family and forms COMPASS complexes with WRAD and menin, among other cofactors, to regulate gene expression, especially genes involved in embryonic development, neuronal and muscle differentiation, and hematopoiesis[2][3]. Through its methyltransferase activity, it maintains active chromatin states at CpG island promoters, protects against DNA methylation, and ensures transcriptional readiness of developmentally regulated genes[1][2]. Mutations or dysregulation in KMT2B are causative for hereditary dystonias and have been implicated in a range of cancers and inflammatory or neurodegenerative conditions[2]. KMT2B is currently considered a promising but challenging therapeutic target in epigenetic and disease modulation, with safety concerns stemming from its central role in gene regulation and development[2].

Other names

Histone-lysine N-methyltransferase 2BKMT2BMLL2MLL4HRX2KIAA0304TRX2WBP7Lysine N-methyltransferase 2BMyeloid/lymphoid or mixed-lineage leukemia protein 4Trithorax homolog 2WW domain-binding protein 7CXXC10DYT28MRD68Mixed lineage leukemia gene homolog 2

Inhibition of H3K4 methyltransferase activity, leading to altered gene expression via reduced H3K4 trimethylation and chromatin remodeling[2][3] Potential reactivation of gene promoters by impacting DNA methylation protection mechanisms[1]