RNA聚合酶II调节拓酶1活动,有利于高效转录
Laura Baranello1, Damian Wojtowicz2, Kairong Cui3
1Laboratory of Pathology, NCI/NIH, Bethesda, MD 20892, USA.
Cell
|April 9, 2016
概括
转录机器直接控制了拓酶1 (TOP1) 的活性. 在RNA聚合酶II (RNAPII) 暂停释放后,BRD4激酶活性刺激TOP1,在转录过程中管理DNA拓.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- DNA拓对于DNA复制和转录至关重要.
- 拓酶1 (TOP1) 通过管理超级卷曲来调节DNA拓.
- 在转录启动和延长过程中,RNA聚合酶II (RNAPII) 的活性受到严格调节.
研究的目的:
- 阐明转录机器控制TOP1活动的机制.
- 研究BRD4在转录过程中调节TOP1活动中的作用.
- 了解DNA拓在整个转录周期中是如何管理的.
主要方法:
- 染色体免疫沉测序 (ChIP-seq) 来绘制TOP1占用率.
- 拓酶1测序 (TOP1-seq) 来映射触媒参与的TOP1.
- 分析RNAPII基终端域 (CTD) 酸化和BRD4激酶活性.
主要成果:
- 只有在RNAPII暂停释放后,TOP1才能对促进体完全活跃.
- 化RNAPIICTD和BRD4激酶活动刺激TOP1活动和过程性.
- 通过BRD4介导的TOP1刺激可以克服对抗转录的扭曲应力,同时保持促进体近位负超线圈.
结论:
- 转录机制通过BRD4和RNAPII酸化直接控制TOP1活动.
- 这种协调的行动确保了有效的转录延长,同时保持了调节性DNA拓.
- 这些发现提供了针对病态基因表达的新策略.
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