| Autor: |
Zhao, Hui, Liu, Lin-Lin, Sun, Jian, Jin, Lian, Xie, Hai-Bing, Li, Jian-Bo, Xu, Hui, Wu, Dong-Dong, Zhuang, Xiao-Lin, Peng, Min-Sheng, Guo, Ya-Jun, Qian, Wei-Zhu, Otecko, Newton O., Sun, Wei-Jie, Qu, Liang-Hu, He, Jie, Chen, Zhao-Li, Liu, Rong, Chen, Ce-Shi, Zhang, Ya-Ping |
| Zdroj: |
SCIENCE CHINA Life Sciences; April 2024, Vol. 67 Issue: 4 p765-777, 13p |
| Abstrakt: |
Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8Bgene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8Bgene as compared with orthologs in macaques. In addition, over-expression TBC1D8Bpromoted cell proliferation and migration through “a dual finger” catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitroand knockdown of TBC1D8Battenuated tumorigenesis in vivo.Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8Bgene. These findings provide a significant insight into the effects of human-specific insertions on evolution. |
| Databáze: |
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