Suv39h1, a lysine methyltransferase, is known for its role in introducing di-and trimethylation at histone H3 lysine 9 (H3K9), which is crucial for maintaining heterochromatin and gene repression. It consists of a catalytic SET domain and a chromodomain, and is involved in various biological pathways. Its study using genetic models like gene knockout (KO) and conditional knockout (CKO) mouse models has been valuable in understanding its functions [6].

In liver fibrosis, HSC-specific or myofibroblast-specific deletion of Suv39h1 in mice ameliorated liver fibrosis. Suv39h1 inhibition by chaetocin also mitigated liver fibrosis in mice. Mechanistically, Suv39h1 bound to the promoter of heme oxygenase 1 (HMOX1) and repressed its transcription [1]. In adoptive T-cell therapies, genetic disruption of SUV39H1 enhanced the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. In solid tumor models, inactivation of SUV39H1 in 41BB-based CAR T cells enhanced their long-term persistence, protecting mice against tumor relapses and rechallenges [2,3]. In limb ischemia mice models, pharmaceutical inhibition or genetic deletion of SUV39H1 significantly improved blood perfusion, capillary density, and angiogenesis in ischemic muscle tissue [4]. In liver ischemia-reperfusion injury, global or hepatocyte conditional Suv39h1 KO mice were protected from liver I/R injury [5].

In conclusion, Suv39h1 is essential in maintaining heterochromatin and gene repression. Model-based research, especially KO/CKO mouse models, has revealed its roles in diseases such as liver fibrosis, cancer (leukemia, prostate cancer, solid tumors, glioblastoma), limb ischemia, and liver ischemia-reperfusion injury. These findings offer potential therapeutic targets for these disease areas.