SUV39H2, also known as KMT1B, is a member of the SUV39 subfamily of lysine methyltransferases. It plays a significant role in histone H3-K9 di-/tri-methylation, transcriptional regulation, and cell cycle. Its activities are crucial for maintaining heterochromatin and gene repression, and it is involved in various biological processes [2,6].

In degenerated nucleus pulposus cells, SUV39H2-mediated K141 mono-methylation of PPP1CA disrupts TFEB-dependent autophagy, promoting intervertebral disc degeneration [1]. In trophoblast stem cells, SUV39H2 contributes to cell maintenance and restrains differentiation, and its disruption leads to cell proliferation arrest and differentiation activation [3]. In cardiomyocytes, knockdown of SUV39H2 accelerates senescence, while overexpression inhibits this phenotype, protecting cardiomyocytes from oxidative stress-induced damage through the p53-BTG2 pathway [4]. In gastric cancer, SUV39H2 promotes proliferation, inhibits apoptosis, and reduces chemosensitivity by promoting homologous recombination through epigenetic repression of DUSP6 [5]. In epidermal stem and progenitor cells, loss of SUV39H2 function relieves gene repression, enhancing Wnt activity and causing premature cell cycle exit [7]. Ablation of SUV39H2 in hepatocytes attenuates non-alcoholic steatohepatitis (NASH) in mice by regulating Vanin-1 transcription [8]. In osteosarcoma cells, knockdown of SUV39H2 suppresses cancer cell growth, viability, and induces apoptosis [9].

In summary, SUV39H2 is essential for multiple biological processes and is involved in various disease conditions. Through gene-knockout or conditional-knockout mouse models and other loss-of-function experiments, we have learned that SUV39H2 is implicated in diseases such as intervertebral disc degeneration, NASH, and several types of cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Liang, Huaizhen, Luo, Rongjin, Li, Gaocai, Song, Yu, Yang, Cao. 2023. Lysine methylation of PPP1CA by the methyltransferase SUV39H2 disrupts TFEB-dependent autophagy and promotes intervertebral disc degeneration. In Cell death and differentiation, 30, 2135-2150. doi:10.1038/s41418-023-01210-4. https://pubmed.ncbi.nlm.nih.gov/37605006/

2. Li, Baihui, Zheng, Yu, Yang, Lili. 2019. The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View. In Journal of Cancer, 10, 721-729. doi:10.7150/jca.28254. https://pubmed.ncbi.nlm.nih.gov/30719171/

3. Wang, Lei, Chakraborty, Damayanti, Iqbal, Khursheed, Soares, Michael J. 2021. SUV39H2 controls trophoblast stem cell fate. In Biochimica et biophysica acta. General subjects, 1865, 129867. doi:10.1016/j.bbagen.2021.129867. https://pubmed.ncbi.nlm.nih.gov/33556426/

4. Wang, Kan, Zhu, Qiang Zhang, Ma, Xian Tao, Cheng, Cai. 2021. SUV39H2/KMT1B Inhibits the cardiomyocyte senescence phenotype by down-regulating BTG2/PC3. In Aging, 13, 22444-22458. doi:10.18632/aging.203551. https://pubmed.ncbi.nlm.nih.gov/34559682/

5. Yang, Jing, Xu, Penghui, Chen, Zetian, Li, Bowen, Xu, Zekuan. 2023. N6-methyadenosine modified SUV39H2 regulates homologous recombination through epigenetic repression of DUSP6 in gastric cancer. In Cancer letters, 558, 216092. doi:10.1016/j.canlet.2023.216092. https://pubmed.ncbi.nlm.nih.gov/36806557/

6. Weirich, Sara, Khella, Mina S, Jeltsch, Albert. 2021. Structure, Activity and Function of the Suv39h1 and Suv39h2 Protein Lysine Methyltransferases. In Life (Basel, Switzerland), 11, . doi:10.3390/life11070703. https://pubmed.ncbi.nlm.nih.gov/34357075/

7. Balmer, Pierre, Hariton, William V J, Sayar, Beyza S, Roosje, Petra, Müller, Eliane J. . SUV39H2 epigenetic silencing controls fate conversion of epidermal stem and progenitor cells. In The Journal of cell biology, 220, . doi:10.1083/jcb.201908178. https://pubmed.ncbi.nlm.nih.gov/33604655/

8. Wu, Shiqiang, Ren, Wenjing, Hong, Jiameng, Yang, Yuyu, Lu, Yunjie. 2024. Ablation of histone methyltransferase Suv39h2 in hepatocytes attenuates NASH in mice. In Life sciences, 343, 122524. doi:10.1016/j.lfs.2024.122524. https://pubmed.ncbi.nlm.nih.gov/38401627/

9. Piao, Lianhua, Yuan, Xiaofeng, Zhuang, Ming, Kong, Ren, Liu, Zhiwei. 2018. Histone methyltransferase SUV39H2 serves oncogenic roles in osteosarcoma. In Oncology reports, 41, 325-332. doi:10.3892/or.2018.6843. https://pubmed.ncbi.nlm.nih.gov/30542727/