通过真核生物激活剂进行转录协同作用的一般机制
T Chi1, P Lieberman, K Ellwood
1Department of Biological Chemistry, University of California, Los Angeles, School of Medicine 90095-1737, USA.
激活剂的协同基因激活涉及TFIID:TFIIA复合体的稳定组装. 在预启动复合体形成的这个早期步骤通过招募TFIIB来增强转录活动.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 病毒学 病毒学
背景情况:
- 细胞基因表达依赖于作为模块的RNA聚合酶II促进体和上游激活体.
- 这些模块的协同作用调节了基因转录.
- 泽布拉是一种爱斯坦-巴尔病毒 (EBV) 激活剂,为研究非酸性激活剂协同作用提供了一个模型.
研究的目的:
- 通过激活剂调解的转录协同作用的生化机制的研究.
- 确定TFIID:TFIIA (DA) 复合组合在协同基因激活中的作用.
- 探索酸性和非酸性激活剂的统一机制.
主要方法:
- 对ZEBRA和GAL4-VP16激活剂的生物化学分析.
- DNase I 足迹测定试验.
- 凝转移试验用于研究蛋白质-DNA相互作用.
主要成果:
- 协同转录效应与TFIID:TFIIA (DA) 复合体的组合相关.
- 激活剂依赖的DA复合体表现出稳定的TFIIB结合,受TAFs的调节.
- 通过增加复杂的稳定性,TFIIB绑定增强了协同作用.
- 对于酸性激活剂GAL4-VP16也观察到类似的机制.
结论:
- 提出了通过多种激活剂实现基因激活和协同作用的统一机制.
- 转录调节中的协同作用在预启动复合组合的初始阶段表现出来.
- 对于协同基因激活来说,TFIIB对TFIID:TFIIA复合体的稳定招募至关重要.
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