母体TDP-43与RNA Pol II相互作用,并调节胚胎基因组激活
Xiaoqing Nie1,2, Qianhua Xu3,4, Chengpeng Xu1,2
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Stem Cell and Regeneration, Beijing Institute of Stem Cell and Regenerative Medicine, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Nature communications
|July 17, 2023
概括
母体TDP-43蛋白对小鼠早期胚胎发育至关重要. 它通过与RNA聚合酶II相互作用来调节细胞体基因组激活 (ZGA),确保胚胎发生的适当基因表达.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 卵巢基因组激活 (ZGA) 是胚胎早期发育的一个关键步骤,标志着从母体控制到卵巢控制的过渡.
- 在哺乳动物中调节ZGA的精确分子机制尚未完全理解.
- 一种DNA结合蛋白TDP-43在RNA处理中已知作用,但其在早期胚胎发生过程中的功能尚不清楚.
研究的目的:
- 研究母体TDP-43在哺乳动物早期胚胎发育中的作用.
- 阐明TDP-43调节ZGA的机制.
- 为了确定TDP-43与关键的转录机制的相互作用.
主要方法:
- 产妇TDP-43淘汰赛小鼠模型的生成.
- 免疫光显微镜用于追踪TDP-43的定位.
- 染色体免疫沉 (ChIP) 用于评估基因促进者的Pol II占用率.
- 生物化学分析以确定TDP-43的相互作用伙伴.
主要成果:
- 母体TDP-43对于小鼠胚胎发育至关重要,缺少它会导致双细胞阶段的停止.
- 在小到主要ZGA转换过程中,TDP-43转移到核中,并与RNA聚合酶II (Pol II) 在ZGA基因促进器上同定位.
- TDP-43与Pol II子单元 (Polr2a) 和Cyclin T1相互作用,其耗尽会影响Pol II的招募和ZGA.
- 失去母体TDP-43会导致缺陷的ZGA和胚胎发育失败.
结论:
- 孕产妇TDP-43是小鼠中ZGA的关键调节者.
- TDP-43通过确保适当的RNA Pol II配置和功能在目标基因促进器上促进ZGA.
- 这项研究突出了TDP-43在通过转录调节协调早期胚胎发育中的新作用.
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