Ezh1, an epigenetic silencing factor, is a core component of polycomb repressive complex 2 (PRC2). It functions as a histone methyltransferase, mediating the mono-, di- and tri-methylation of histone H3 lysine 27 (H3K27me1/2/3), and is crucial for the growth and differentiation of cells [1,3]. Ezh1 is involved in multiple biological pathways and its dysregulation has implications in various diseases. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its function.

In iPSC-derived T cell differentiation, Ezh1 repression promotes in vitro differentiation and maturation of T cells from iPSCs. EZ-T cells generated through Ezh1-knockdown-mediated epigenetic reprogramming show a diverse T cell receptor repertoire and mature molecular signatures, and exhibit potent antitumor activities when transduced with chimeric antigen receptors [2]. In oocyte meiosis prophase I in mice, Ezh1/2 deficiency leads to cell apoptosis, reduction in oocyte numbers, failure of DNA double-strand breaks repair, and break of meiotic progression. Ezh1/2 deletion also affects the expression of mitochondrial related genes in MII oocytes and early embryos [4]. In neurogenesis, loss-of-function variants in Ezh1 disrupt neural progenitor cell differentiation in the developing chick embryo neural tube, and variants in human pluripotent stem cell-derived neural cultures and forebrain organoids perturb cortical neuron differentiation [5].

In conclusion, Ezh1 is essential for processes like cell growth, differentiation, T cell development, oocyte meiosis, and neurogenesis. KO/CKO mouse models have been instrumental in revealing its role in these biological processes and associated disease conditions, such as in cancer, oocyte-related disorders, and neurodevelopmental disorders [2,4,5].

References:

1. An, Ran, Li, Yu-Qing, Lin, Yue-Ling, Li, Man-Mei, Liu, Zhong. 2022. EZH1/2 as targets for cancer therapy. In Cancer gene therapy, 30, 221-235. doi:10.1038/s41417-022-00555-1. https://pubmed.ncbi.nlm.nih.gov/36369341/

2. Jing, Ran, Scarfo, Irene, Najia, Mohamad Ali, Maus, Marcela V, Daley, George Q. . EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity. In Cell stem cell, 29, 1181-1196.e6. doi:10.1016/j.stem.2022.06.014. https://pubmed.ncbi.nlm.nih.gov/35931029/

3. Lee, Soo Hyun, Li, Yingying, Kim, Hanbyeol, Park, Kyumin, Lee, Chul-Hwan. . The role of EZH1 and EZH2 in development and cancer. In BMB reports, 55, 595-601. doi:. https://pubmed.ncbi.nlm.nih.gov/36476271/

4. Jiang, Ting, Zhang, Chengxiu, Cao, Xinjing, Wang, Haibin, Lu, Zhongxian. 2024. EZH1/2 plays critical roles in oocyte meiosis prophase I in mice. In Biological research, 57, 83. doi:10.1186/s40659-024-00564-4. https://pubmed.ncbi.nlm.nih.gov/39511641/

5. Gracia-Diaz, Carolina, Zhou, Yijing, Yang, Qian, Martínez-Balbás, Marian A, Akizu, Naiara. 2023. Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders. In Nature communications, 14, 4109. doi:10.1038/s41467-023-39645-5. https://pubmed.ncbi.nlm.nih.gov/37433783/