通过多能细胞中的核受体进行线粒体书签冗余
Almira Chervova1,2, Amandine Molliex1,2, H Irem Baymaz3
1Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, Paris, France.
Nature structural & molecular biology
|January 10, 2024
概括
线粒体书签转录因子 (TFs) 确保细胞分裂后的快速基因重新激活. 像ESRRB和NR5A2这样的核受体之间的冗余性为细胞周期重新进入期间的基因调节提供了强度.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 假设转录因子 (TFs) 能够促进神经分裂后的快速基因重激活.
- 个人书签TF的丢失往往导致有限的目标基因放松管制,质疑它们的功能意义.
研究的目的:
- 研究核受体ESRRB在线粒体书签中的作用.
- 探索核受体中书签活动的潜在冗余性.
- 确定ESRRB和NR5A2联合活性对基因活性和多能性维持的影响.
主要方法:
- 有针对性的蛋白质组学,以确定ESRB的线粒结合伙伴.
- 专注于核受体NR5A2由于其在多能性中的作用.
- 在线细胞退出过程中ESRRB和NR5A2的同时降解,以评估目标基因的转录活性.
主要成果:
- 确定了核受体之间线粒结合的显著冗余,包括ESRRB和NR5A2.2.
- 证明ESRRB和NR5A2在许多活性基因的促进剂和增强剂上的联合书签活动.
- 观察到数百个ESRRB/NR5A2线性标在它们同时降解时的减弱的转录活性,包括关键多能性因子.
结论:
- 转录因子,特别是核受体的线粒体书签冗余性,增强了基因调控网络在线粒体分裂后的恢复的稳定性.
- 通过线粒体书签,ESRB和NR5A2在维持多能性方面发挥着至关重要的,冗余的作用.
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