一个DNA修复复合体在胚胎干细胞中作为Oct4/Sox2联合激活剂起作用
Yick W Fong1, Carla Inouye, Teppei Yamaguchi
1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|October 4, 2011
概括
研究人员发现了一种干细胞协作激活复合物 (SCC),被确定为XPC核酸切除修复复合物,对于维持胚胎干细胞多能性和重编程至关重要. 这种复合体对于激活涉及多能性的关键基因至关重要.
科学领域:
- * 分子和细胞生物学
- * * 干细胞生物学
- *表观遗传学和基因调控
背景情况:
- *胚胎干细胞具有多能性,即能够分化为所有细胞类型.
- *转录激活剂Oct4,Sox2和Nanog是多能性的关键调节剂.
- * 同活性剂在调解这些转录因子的功能方面发挥着关键作用.
研究的目的:
- * 确定参与Oct4/Sox2介导的多能性基因表达程序的新型协活性剂.
- * 描述新发现的一种干细胞协激活体 (SCC) 的功能和作用机制.
主要方法:
- *采用无偏见的体外转录生物化学补充试验来发现SCC.
- *利用净化,质谱和复制来识别SCC组件.
- *研究了SCC与Oct4/Sox2的相互作用,并使用ChIP-seq.对其招募以准基因促进体.
- *评估了SCC枯竭对ES细胞多能性和体细胞重编程的影响.
主要成果:
- * 发现了一种多子单元干细胞协同激活复合体 (SCC),对于Oct4和Sox2.2对Nanog基因的协同激活至关重要.
- * 确定SCC为三元体XPC核酸切除修复复合体.
- *已证明SCC与Oct4和Sox2的直接相互作用,并将其招募到多能性基因促进剂中.
- * 表明SCC/XPC枯竭会影响ES细胞多能性和体细胞重编程到诱导多能干细胞 (iPS) 细胞.
结论:
- *XPC核酸切除修复复合体作为关键干细胞协活性剂 (SCC) 起作用.
- *SCC在维持胚胎干细胞多能性和促进体细胞重编程方面发挥着至关重要的作用.
- * 这一发现揭示了XPC复合体在转录调节和基因组完整性方面的双重作用.
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