Euchromatic histone lysine methyltransferase 1 (EHMT1)

Euchromatic histone lysine methyltransferase 1 (EHMT1) is an enzyme encoded by the EHMT1 gene located on chromosome 9. This SET-domain containing protein catalyzes mono- and dimethylation of lysine 9 on histone H3 (producing H3K9me1 and H3K9me2), a modification marking transcriptionally repressed chromatin in euchromatic regions[1][4][5]. EHMT1 forms heteromeric complexes with G9a (EHMT2), acting as a key epigenetic regulator of gene silencing during development and cell cycle progression[4][5]. It is involved in silencing MYC- and E2F-responsive genes in G0/G1 transition and also methylates non-histone substrates, including lysine 373 of p53/TP53[1][4]. Germline mutations or deletions in EHMT1 cause Kleefstra syndrome, a neurodevelopmental disorder. Dysregulation of EHMT1 and associated histone methyl marks has also been implicated in oncogenesis and general chromatin misregulation[1][3][5][6]. There are no approved drugs directly targeting EHMT1, but several research inhibitors exist, and it is considered a promising epigenetic drug target.

Other names

G9a-like proteinGLPHistone-lysine N-methyltransferase EHMT1Lysine N-methyltransferase 1DEu-HMTase1KMT1DFP13812KLEFS1GLP1EHMT1-IT1EUHMTASE1

Inhibition of lysine methyltransferase activity (primarily H3K9 mono- and dimethylation); Epigenetic modulation leading to derepression of specific gene sets