Euchromatic histone-lysine N-methyltransferase 1 (EHMT1) (EHMT1)

Euchromatic histone-lysine N-methyltransferase 1 (EHMT1), also known as GLP (G9a-like protein), is a key epigenetic enzyme that catalyzes the mono- and dimethylation of Lysine 9 on Histone H3 (H3K9me1 and H3K9me2) [UniProt: Q9HDC1]. These modifications are critical for the formation of repressive euchromatin and the silencing of specific genes during development [PubMed: 21835041]. EHMT1 typically functions as a heteromeric complex with its paralog EHMT2 (G9a), and this complex is essential for maintaining genomic stability and regulating neuronal plasticity [PubMed: 16402357]. Mutations or deletions in the EHMT1 gene are the primary cause of Kleefstra syndrome, a neurodevelopmental disorder characterized by intellectual disability and distinct facial features [NIH: GeneReviews NBK1116]. In oncology, EHMT1 is often overexpressed and contributes to the silencing of tumor suppressor genes, making it a target for small-molecule inhibitors like UNC0638 and UNC0642 in cancer therapy research [PubMed: 22813531]. These inhibitors work by competing with the substrate binding site, thereby reducing H3K9 methylation levels and restoring gene expression [PubMed: 30104615].

Other names

GLPG9a-like proteinKMT1DEu-HMTase1Histone-lysine N-methyltransferase, H3 lysine-9 specific 5

Inhibition of histone methyltransferase activity, specifically preventing the mono- and dimethylation of Lysine 9 on Histone H3 (H3K9me1/2) to modulate gene expression.