Suv39h1, a lysine methyltransferase, is known for its role in introducing di-and trimethylation at histone H3 lysine 9 (H3K9). This modification is crucial for maintaining heterochromatin and gene repression. It functions within epigenetic regulatory pathways, which are fundamental for various biological processes such as cell differentiation, development, and disease-related mechanisms [4]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, have been invaluable in studying Suv39h1.

In liver fibrosis, HSC-specific or myofibroblast-specific deletion of Suv39h1 in mice (achieved by crossbreeding Suv39h1 f/f mice with Lrat-Cre or Postn-CreERT2 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. Transcriptional and genome accessibility profiling showed improved expression and accessibility of memory transcription factors in SUV39H1-edited CAR T cells [2]. Also, inactivation of SUV39H1 in BBz-CAR T cells enhanced their long-term persistence, protecting mice against tumor relapses and rechallenges in lung and disseminated solid tumor models [3].

In conclusion, Suv39h1 is a key epigenetic regulator involved in maintaining heterochromatin and gene repression. KO/CKO mouse models have revealed its significance in diseases such as liver fibrosis, and in enhancing the efficacy of adoptive T-cell therapies for cancer. These findings offer potential therapeutic targets for treating liver cirrhosis and improving cancer immunotherapies.