Euchromatic histone-lysine N-methyltransferase 1 and 2 (EHMT1 (GLP), EHMT2 (G9a))

EHMT1 (GLP) and EHMT2 (G9a) are highly related protein lysine methyltransferases that primarily act as a heterodimeric complex to methylate lysine 9 on histone H3, leading to chromatin condensation and transcriptional repression. They also methylate non-histone substrates and are crucial in processes such as transcriptional regulation, maintenance of genome methylation, and DNA repair. Genetic or pharmacological inhibition of EHMT1/2 leads to increased cancer cell sensitivity to chemotherapy, impacts DNA replication and repair, and can potentiate anti-tumor immune responses by upregulating genes such as STING. EHMT1/2 are therefore considered therapeutic targets in cancer and other diseases involving epigenetic dysregulation. Note: EHMT1 and EHMT2 are distinct genes/proteins, but often function together in biological contexts and are drugged together using broad-spectrum inhibitors.

Other names

EHMT1: GLP, KMT1DEHMT2: G9a, KMT1C

Inhibition of histone H3 lysine 9 (H3K9) methylation Disruption of transcriptional repression of tumor suppressor genes Induction of replication stress and DNA damage signals Modulation of immune gene expression (e.g., increased STING expression)