Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) (EHMT2)

Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), commonly referred to as G9a, is a primary enzyme responsible for the mono- and dimethylation of Lysine 9 on Histone H3 (H3K9me1 and H3K9me2) in euchromatic regions (UniProt: Q96KQ7). This epigenetic modification is a hallmark of transcriptional repression and plays a critical role in maintaining gene silencing and heterochromatin formation (PubMed: 11525730). Beyond its catalytic activity, EHMT2 often functions within a multimeric complex, including EHMT1 (GLP), and interacts with DNA methyltransferases to coordinate epigenetic silencing (PubMed: 15927959). In oncology, EHMT2 is frequently overexpressed in various cancers, including lung, breast, and colon cancer, where it promotes tumor cell proliferation, epithelial-mesenchymal transition, and suppression of tumor suppressor genes (PubMed: 24618898). Consequently, EHMT2 has emerged as a significant therapeutic target, with several small-molecule inhibitors like UNC0638 and A-366 developed to reverse repressive histone marks and restore normal gene expression patterns (PubMed: 21743462). Research also indicates its involvement in neurological processes such as memory formation and drug addiction, expanding its potential clinical relevance beyond oncology (PubMed: 20080668).

Other names

G9a (UniProt: Q96KQ7)Histone-lysine N-methyltransferase EHMT2 (UniProt: Q96KQ7)HLA-B-associated transcript 8 (UniProt: Q96KQ7)BAT8 (UniProt: Q96KQ7)KMT1C (UniProt: Q96KQ7)NG36 (UniProt: Q96KQ7)G9A (UniProt: Q96KQ7)

Competitive inhibition of the S-adenosyl-L-methionine (SAM) binding site or the substrate binding site of the SET domain, leading to reduced dimethylation of Lysine 9 on Histone H3 (H3K9me2) (PubMed: 21743462).