Euchromatic histone-lysine N-methyltransferase 1 (EHMT1 (often also called GLP/G9a-like protein))

Euchromatic histone-lysine N-methyltransferase 1 (EHMT1), also known as G9a-like protein (GLP), is an enzyme encoded by the EHMT1 gene. It mono- and dimethylates lysine 9 on histone H3 (H3K9me1 and H3K9me2), marking chromatin for transcriptional repression and recruiting heterochromatin protein complexes. EHMT1 works both as a homodimer and as a heterodimer with EHMT2 (G9a), playing a central role in epigenetic silencing, chromatin structure, genome stability, and proper development—especially neuronal differentiation and maintenance. Germline mutations or deletions in EHMT1 cause Kleefstra syndrome, a disorder characterized by intellectual disability, developmental delay, and autistic traits. EHMT1 also participates in the DNA damage response and is implicated in cancer, where its activity can contribute to resistance to chemotherapy and abnormal gene silencing. Inhibitors of EHMT1/2 are of research interest for reversing epigenetic silencing in cancer and potentially other diseases, but therapeutic targeting requires careful monitoring due to roles in normal tissue maintenance and development.

Other names

GLPG9a-like proteinKMT1DEu-HMTase1FLJ12879KIAA1876bA188C12.1FLJ40292EHMT1-IT1

Inhibitors block enzymatic methylation of histone H3 lysine 9 (H3K9me1/me2), leading to altered gene expression and increased DNA damage/defective DNA repair in certain cancer models Inhibition can reduce recruitment of repressive chromatin modifiers, disrupt DNA methylation maintenance, and derepress silenced genes