| Autor: |
Wang, Mengting, Wang, Liping, Huang, Yanxin, Qiao, Zhibin, Yi, Shanru, Zhang, Weina, Wang, Jing, Yang, Guang, Cui, Xinyu, Kou, Xiaochen, Zhao, Yanhong, Wang, Hong, Jiang, Cizhong, Gao, Shaorong, Chen, Jiayu |
| Zdroj: |
SCIENCE CHINA Life Sciences; October 2024, Vol. 67 Issue: 10 p2132-2148, 17p |
| Abstrakt: |
The TET family is well known for active DNA demethylation and plays important roles in regulating transcription, the epigenome and development. Nevertheless, previous studies using knockdown (KD) or knockout (KO) models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles, as well as compensatory effects among TET family members, which has made the understanding of the enzymatic role of TET not accurate enough. To solve this problem, we successfully generated mice catalytically inactive for specific Tetmembers (Tetm/m). We observed that, compared with the reported KO mice, mutant mice exhibited distinct developmental defects, including growth retardation, sex imbalance, infertility, and perinatal lethality. Notably, Tetm/mmouse embryonic stem cells (mESCs) were successfully established but entered an impaired developmental program, demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA methylation. Intriguingly, Tet3, traditionally considered less critical for mESCs due to its lower expression level, had a significant impact on the global hydroxymethylation, gene expression, and differentiation potential of mESCs. Notably, there were common regulatory regions between Tet1and Tet3in pluripotency regulation. In summary, our study provides a more accurate reference for the functional mechanism of Tethydroxymethylase activity in mouse development and ESC pluripotency regulation. |
| Databáze: |
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