Regulatory interplay between TFIID's conformational transitions and its modular interaction with core promoter DNA.
Regulatory interplay between TFIID's conformational transitions and its modular interaction with core promoter DNA.
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DOI：
10.4161/trns.25291
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Nogales E
中科院分区：
文献类型：
--
作者：
Cianfrocco MA;Nogales E
最近的人类TFIID的结构和生物化学研究显着增加了我们的理解TFIID的募集启动子DNA及其在转录起始中的作用的机制。使用cryo-EM的结构研究表明，模块化的相互作用的基础TFIID的能力，同时结合多个启动子基序，并定义一个DNA状态，这将有利于转录起始。在这里，我们提出了一个通用的模型启动子结合TFIID，其中共激活剂，激活剂，和组蛋白修饰促进和/或稳定的构象状态TFIID的核心启动子参与的结果。在这种高亲和力的构象，我们建议，TFIID的广泛的相互作用与启动子DNA导致的拓扑结构的变化，促进RNAP II的最终加载的DNA。虽然需要更多的工作来剖析激活剂和抑制剂对TFIID的DNA结合的单独贡献，但最近的cryo-EM研究提供了一个物理框架来指导未来的结构，生物物理和生物化学实验。
Recent structural and biochemical studies of human TFIID have significantly increased our understanding of the mechanisms underlying the recruitment of TFIID to promoter DNA and its role in transcription initiation. Structural studies using cryo-EM revealed that modular interactions underlie TFIID’s ability to bind simultaneously multiple promoter motifs and to define a DNA state that will facilitate transcription initiation. Here we propose a general model of promoter binding by TFIID, where co-activators, activators, and histone modifications promote and/or stabilize a conformational state of TFIID that results in core promoter engagement. Within this high affinity conformation, we propose that TFIID’s extensive interaction with promoter DNA leads to topological changes in the DNA that facilitate the eventual loading of RNAP II. While more work is required to dissect the individual contributions of activators and repressors to TFIID’s DNA binding, the recent cryo-EM studies provide a physical framework to guide future structural, biophysical, and biochemical experiments.