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Chromatin Fiber Invasion and Nucleosome Displacement by the Rap1 Transcription Factor.
Molecular Cell ( IF 14.5 ) Pub Date : 2019-11-21 , DOI: 10.1016/j.molcel.2019.10.025
Maxime Mivelaz 1 , Anne-Marinette Cao 1 , Slawomir Kubik 2 , Sevil Zencir 2 , Ruud Hovius 1 , Iuliia Boichenko 1 , Anna Maria Stachowicz 2 , Christoph F Kurat 3 , David Shore 2 , Beat Fierz 1
Affiliation  

Pioneer transcription factors (pTFs) bind to target sites within compact chromatin, initiating chromatin remodeling and controlling the recruitment of downstream factors. The mechanisms by which pTFs overcome the chromatin barrier are not well understood. Here, we reveal, using single-molecule fluorescence, how the yeast transcription factor Rap1 invades and remodels chromatin. Using a reconstituted chromatin system replicating yeast promoter architecture, we demonstrate that Rap1 can bind nucleosomal DNA within a chromatin fiber but with shortened dwell times compared to naked DNA. Moreover, we show that Rap1 binding opens chromatin fiber structure by inhibiting inter-nucleosome contacts. Finally, we reveal that Rap1 collaborates with the chromatin remodeler RSC to displace promoter nucleosomes, paving the way for long-lived bound states on newly exposed DNA. Together, our results provide a mechanistic view of how Rap1 gains access and opens chromatin, thereby establishing an active promoter architecture and controlling gene expression.

中文翻译:

Rap1 转录因子对染色质纤维的侵袭和核小体置换。

先锋转录因子 (pTF) 与致密染色质内的靶位点结合,启动染色质重塑并控制下游因子的募集。pTF 克服染色质屏障的机制尚不清楚。在这里,我们使用单分子荧光揭示了酵母转录因子 Rap1 如何侵入和重塑染色质。使用复制酵母启动子结构的重组染色质系统,我们证明 Rap1 可以结合染色质纤维内的核小体 DNA,但与裸 DNA 相比,停留时间缩短。此外,我们表明 Rap1 结合通过抑制核小体间接触打开染色质纤维结构。最后,我们揭示了 Rap1 与染色质重塑器 RSC 合作取代启动子核小体,为新暴露的 DNA 上的长寿命结合状态铺平了道路。总之,我们的结果提供了一个关于 Rap1 如何获得访问和打开染色质,从而建立一个活跃的启动子结构和控制基因表达的机制观点。
更新日期:2019-11-22
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