转录因子通过其激活域的相分离能力激活基因
Ann Boija1, Isaac A Klein2, Benjamin R Sabari1
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cell
|November 20, 2018
概括
多种转录因子 (TFs) 使用它们的激活域 (ADs) 与Mediator,一个关键的联合激活剂形成相分离的凝聚物. 这种凝结物形成对基因激活至关重要,正如OCT4,GCN4和雌激素受体的研究表明的那样.
科学领域:
- 分子生物学
- 基因调控
背景情况:
- 转录因子 (TF) 通过DNA结合域 (DBD) 和激活域 (AD) 调节基因表达.
- ADs调解基因激活的机制在很大程度上仍未被描述.
研究的目的:
- 通过检查它们与Mediator联合激活剂的相互作用来研究ADs在基因激活中的作用.
- 确定相隔是否是一种AD与调解器相互作用的机制.
主要方法:
- 使用纯化的蛋白质进行体外分离试验.
- 在体内基因激活测试.
- 位点定向的突变发生,以确定关键氨基酸残留物.
主要成果:
- 多种转录因子ADs与介质协活性剂形成相分离的凝聚物.
- 对于OCT4和GCN4,体内基因激活和体内介质凝聚物形成取决于相同的氨基酸残留物.
- 雌激素增强了雌激素受体AD和Mediator之间的相分离,与增强的基因激活相关.
结论:
- 抗体的相隔能力是与Mediator相互作用的保存机制.
- 中介-TF凝聚物的形成直接参与调节基因激活.
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