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 contains a catalytic SET domain and a chromodomain, and is involved in multiple biological pathways. Genetic models, such as KO/CKO mouse models, have been valuable in studying its functions [7].

In liver fibrosis, HSC-specific or myofibroblast-specific deletion of Suv39h1 in mice ameliorated liver fibrosis. Suv39h1 expression was upregulated during HSC-myofibroblast transition, and its knockdown blocked this transition in vitro. 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 antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. It also optimized the long-term functional persistence of BBz-CAR T cells in solid tumor models, protecting against relapses and rechallenges [2,3].

In limb ischemia of mice, pharmaceutical inhibition or genetic deletion of SUV39H1 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 the injury [5].

In MLL-AF9-induced acute myeloid leukemia, Suv39h1 overexpression increased leukemia latency and decreased the frequency of LSCs, while knockdown accelerated disease progression [6].

In glioblastoma, knockdown of SUV39H1 in patient-derived GSCs impaired their proliferation and stemness, and targeting SUV39H1 in vivo inhibited GSC-driven tumor formation [8].

In summary, Suv39h1 plays essential roles in multiple biological processes and disease conditions. KO/CKO mouse models have been instrumental in revealing its functions in diseases like liver fibrosis, cancer, limb ischemia, and liver ischemia-reperfusion injury, offering potential therapeutic targets for these conditions.