在建立多能性的TET1和TET2的NANOG-依赖功能
Yael Costa1, Junjun Ding, Thorold W Theunissen
1Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Nature
|February 12, 2013
概括
研究人员发现了新的NANOG相关蛋白质,包括TET1和TET2,对于增强体细胞重编程至关重要. 这些蛋白质与NANOG物理相互作用,通过催化活性促进多能性建立.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- NANOG是维持多能性和重编程体细胞的关键转录因子.
- 在重新编程过程中NANOG的蛋白质相互作用和功能尚未完全理解.
研究的目的:
- 确定参与体细胞重编程的新型NANOG相互作用蛋白质.
- 阐明这些相互作用在建立天真多能性的作用.
主要方法:
- 利用增强的净化技术和计算算法来识别小鼠胚胎干细胞中的NANOG相互作用体.
- 使用共免疫沉和评估重编程效率确认了物理关联.
- 研究了TET家族蛋白质 (TET1,TET2) 在NANOG介导重编程中的作用.
主要成果:
- 确定了27个高可信度NANOG蛋白合作伙伴,其中包括19个像TET1.1这样的新型相互作用体.
- 证明NANOG在物理上与TET1和TET2相互作用,从而提高重新编程的效率.
- 表明TET1/TET2催化活性对于它们与NANOG的协同重编程效应至关重要.
- 发现NANOG和TET1共同占据了关键的多能性基因位点,TET1的结合取决于NANOG.
结论:
- 在重编程过程中,TET1和TET2是NANOG的新型,功能重要互动合作伙伴.
- NANOG和TET1/TET2之间的物理相互作用通过TET的催化活性促进了重编程.
- NANOG招募TET1以向基因,增加5-基甲基氨酸,并为天真的多能性启动表达.
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