通过增强剂激活来调节促剂-近位暂停释放的PAF1
Fei Xavier Chen1, Peng Xie2, Clayton K Collings1
1Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Science (New York, N.Y.)
|September 2, 2017
概括
基因聚合酶II (Pol II) 暂停调节基因表达. 与Pol II相关的1因子 (PAF1) 蛋白抑制了增强剂的活性,控制了被暂停的基因中的Pol II释放.
科学领域:
- 分子生物学
- 基因调控
- 转录控制
背景情况:
- 多细胞生物 (甲基动物) 的基因表达依赖于RNA聚合酶II (Pol II) 促成者-近位暂停和释放.
- 此前已确定Pol II相关因子1 (PAF1) 是Pol II释放到生产延伸的调节剂.
- PAF1在调节转录增强剂中的确切作用及其对Pol II动态的影响尚不清楚.
研究的目的:
- 研究PAF1在转录增强剂中的功能.
- 确定PAF1与增强剂的相互作用如何影响Pol II的暂停和释放.
- 阐明PAF1调节增强剂控制基因表达的机制.
主要方法:
- 对转录增强剂的PAF1占用率的分析.
- 通过CRISPR调节的PAF1增强剂.
- 使用分子生物学技术评估目标基因促进体的Pol II暂停和释放动力学.
主要成果:
- 发现PAF1占据了转录增强剂并抑制了这些调节元件的一个子集的过度激活.
- 损失PAF1导致其目标增强剂的激活,随后从附近的基因促进剂释放暂停的Pol II.
- 干扰PAF1调节增强剂对目标基因的Pol II释放受损,但没有影响最初的促进剂暂停.
结论:
- 转录增强剂通过控制被暂停的促进体释放的Pol II来调节基因表达起着至关重要的作用.
- 作为一个关键的调节剂,PAF1将增强剂绑定起来以抑制它们的活性,从而影响Pol II的释放.
- 这种PAF1依赖增强机制通过微调从暂停到延长的过渡来提供对基因表达的特定控制层.
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