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Structures and implications of TBP-nucleosome complexes [Biophysics and Computational Biology]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-07-27 , DOI: 10.1073/pnas.2108859118
Haibo Wang 1 , Le Xiong 1 , Patrick Cramer 2
Affiliation  

The TATA box-binding protein (TBP) is highly conserved throughout eukaryotes and plays a central role in the assembly of the transcription preinitiation complex (PIC) at gene promoters. TBP binds and bends DNA, and directs adjacent binding of the transcription factors TFIIA and TFIIB for PIC assembly. Here, we show that yeast TBP can bind to a nucleosome containing the Widom-601 sequence and that TBP–nucleosome binding is stabilized by TFIIA. We determine three cryo-electron microscopy (cryo-EM) structures of TBP–nucleosome complexes, two of them containing also TFIIA. TBP can bind to superhelical location (SHL) –6, which contains a TATA-like sequence, but also to SHL +2, which is GC-rich. Whereas binding to SHL –6 can occur in the absence of TFIIA, binding to SHL +2 is only observed in the presence of TFIIA and goes along with detachment of upstream terminal DNA from the histone octamer. TBP–nucleosome complexes are sterically incompatible with PIC assembly, explaining why a promoter nucleosome generally impairs transcription and must be moved before initiation can occur.



中文翻译:

TBP-核小体复合物的结构和意义[生物物理学和计算生物学]

TATA 盒结合蛋白 (TBP) 在整个真核生物中高度保守,并且在基因启动子处的转录前起始复合物 (PIC) 的组装中起核心作用。TBP 结合并弯曲 DNA,并指导转录因子 TFIIA 和 TFIIB 的相邻结合以进行 PIC 组装。在这里,我们证明酵母 TBP 可以与含有 Widom-601 序列的核小体结合,并且 TFIIA 稳定了 TBP-核小体的结合。我们确定了 TBP-核小体复合物的三种低温电子显微镜 (cryo-EM) 结构,其中两种还含有 TFIIA。TBP 可以与包含 TATA 样序列的超螺旋位置 (SHL) –6 结合,也可以与富含 GC 的 SHL +2 结合。而在没有 TFIIA 的情况下可能会发生与 SHL –6 的结合,仅在 TFIIA 存在下观察到与 SHL +2 的结合,并且伴随着上游末端 DNA 从组蛋白八聚体中脱离。TBP-核小体复合物在空间上与 PIC 组装不相容,这解释了为什么启动子核小体通常会损害转录并且必须在启动之前移动。

更新日期:2021-07-24
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