College of Animal Science and Technology, Yangzhou University, Jiangsu Province Key Laboratory of Animal Breeding and Molecular Design, Yangzhou, Jiangsu, China.
Reproductive Medicine Center, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, Jiangsu, China.
J Cell Physiol. 2019 Apr;234(4):3762-3774. doi: 10.1002/jcp.27139. Epub 2018 Aug 26.
The transcription factor positioning in promoter regions relate to gene regulation, and the level of DNA methylation and histone acetylation also impact the promoter activity. In this study, we tested and verified the core promoter region and key transcription factor of Nanos2 which is a male-critical gene in the differentiation of embryonic stem cells to male germ cells, meanwhile, epigenetic effects by mean of 5-Aza-2'-deoxycytidine (5-Azadc) and Trichostin A (TSA) on the activity of Nanos2 promoter were detected. The results reveal that key transcription factor Foxd3 is a negative regulator of Nanos2, which suggests that loss-of-function of Foxd3 causes strong expression of Nanos2 responsive to large amounts of primordial germ cells and spermatogonial stem cells,whereas its overexpression causes the opposite effect. Furthermore, both 5-Azadc and TSA can provoke responses of Nanos2, but the combination effect of the two is better.
转录因子在启动子区域的定位与基因调控有关，DNA 甲基化和组蛋白乙酰化的水平也会影响启动子的活性。在这项研究中，我们测试并验证了 Nanos2 的核心启动子区域和关键转录因子，Nanos2 是胚胎干细胞向雄性生殖细胞分化过程中的一个关键基因，同时，通过 5-氮杂-2′-脱氧胞苷（5-Azadc）和 Trichostin A（TSA）检测 Nanos2 启动子活性的表观遗传效应。结果表明，关键转录因子 Foxd3 是 Nanos2 的负调控因子，这表明 Foxd3 的功能丧失会导致大量原始生殖细胞和精原干细胞对 Nanos2 的强烈表达，而其过表达则会产生相反的效果。此外，5-Azadc 和 TSA 均可引发 Nanos2 的反应，但两者的联合作用效果更好。
