Comparison of transcriptional initiation by RNA polymerase II across eukaryotic species.
Comparison of transcriptional initiation by RNA polymerase II across eukaryotic species.
复制标题
RNA聚合酶II在真核生物中转录起始的比较。
DOI：
10.7554/elife.67964
复制
发表时间：
2021-09-13
期刊：
影响因子：
7.7
通讯作者：
Struhl K
中科院分区：
文献类型：
--
作者：
Petrenko N;Struhl K
RNA聚合酶(Pol)II转录起始预起始复合体(PIC)由高度保守的一般转录因子组成。然而，对CHIP-SEQ数据集的分析揭示了真核生物物种之间转录启动过程的动力学和成分差异。在酵母中，Mediator与与增强子结合的激活蛋白紧密结合，但它以一种缺乏激酶模块的形式与启动子瞬时结合。相反，在人、鼠和苍蝇细胞中，Mediator及其激酶模块稳定地与启动子结合，但不与激活剂结合部位结合。这表明酵母和后生动物在激活剂和Pol II之间的动态介体桥的性质和稳定的非活性PIC样实体的组成方面有所不同。与酵母一样，哺乳动物启动子上的TATA结合蛋白(TBP)和TBP相关因子(TAFs)的占有率并不是严格相关的。这表明，在PICs中，TFIID不是一个整体，多种形式的TBP影响不同类别基因的启动。在果蝇中，TFIID而不是酵母和哺乳动物，在起始点下游区域相互作用强烈，这与下游启动子元件在该物种中的重要性一致。最后，Taf7和哺乳动物特有的Mediator的Med26亚单位也在PIC下游的POL II停顿区域附近相互作用，但仅在基因亚群中相互作用，通常不在一起。PIC结构和功能的物种差异可能会影响激活因子和抑制因子如何影响转录活性。
The preinitiation complex (PIC) for transcriptional initiation by RNA polymerase (Pol) II is composed of general transcription factors that are highly conserved. However, analysis of ChIP-seq datasets reveals kinetic and compositional differences in the transcriptional initiation process among eukaryotic species. In yeast, Mediator associates strongly with activator proteins bound to enhancers, but it transiently associates with promoters in a form that lacks the kinase module. In contrast, in human, mouse, and fly cells, Mediator with its kinase module stably associates with promoters, but not with activator-binding sites. This suggests that yeast and metazoans differ in the nature of the dynamic bridge of Mediator between activators and Pol II and the composition of a stable inactive PIC-like entity. As in yeast, occupancies of TATA-binding protein (TBP) and TBP-associated factors (Tafs) at mammalian promoters are not strictly correlated. This suggests that within PICs, TFIID is not a monolithic entity, and multiple forms of TBP affect initiation at different classes of genes. TFIID in flies, but not yeast and mammals, interacts strongly at regions downstream of the initiation site, consistent with the importance of downstream promoter elements in that species. Lastly, Taf7 and the mammalian-specific Med26 subunit of Mediator also interact near the Pol II pause region downstream of the PIC, but only in subsets of genes and often not together. Species-specific differences in PIC structure and function are likely to affect how activators and repressors affect transcriptional activity.