SUV39H2, also known as KMT1B, is a member of the SUV39 subfamily of lysine methyltransferases (KMTs). It plays a significant role in histone H3-K9 di-/tri-methylation, transcriptional regulation, and the cell cycle. It is involved in multiple biological processes such as cell fate determination, autophagy regulation, and is also associated with various diseases including cancers, intervertebral disc degeneration, and non-alcoholic steatohepatitis (NASH) [1,2,3].

In SUV39H2-deficient nucleus pulposus cells, increased K141-methylation of PPP1CA disrupts its interaction with TFEB, blocking TFEB dephosphorylation and nuclear translocation, leading to autophagy deficiency and NPC senescence, and promoting intervertebral disc degeneration. Targeting SUV39H2 effectively mitigates NPC senescence and IDD progression [2]. In hepatocytes, ablation of Suv39h2 improved insulin sensitivity and significantly ameliorated NAFLD, as evidenced by reduced lipid accumulation, inflammation, and fibrosis in the liver. RNA-seq uncovered Vanin-1 (Vnn1) as a novel transcriptional target for Suv39h2 [3].

In conclusion, SUV39H2 is crucial for histone H3-K9 methylation-related transcriptional regulation and cell cycle control. Through gene-knockout-based research in relevant models, its roles in intervertebral disc degeneration and NASH have been revealed. Understanding SUV39H2's functions may offer new therapeutic strategies for these diseases.