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Transcription regulation by the Mediator complex
Nature Reviews Molecular Cell Biology ( IF 81.3 ) Pub Date : 2017-12-06 , DOI: 10.1038/nrm.2017.115
Julie Soutourina

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.



中文翻译:

介体复合体对转录的调控

基因表达调控的改变通常与发育性疾病或癌症有关。转录激活是基因表达调控中的关键现象。在所有真核生物中,RNA聚合酶II转录通常需要RNA聚合酶II转录的介体(Mediator),它是具有模块化组织的大型复合体,它调节该过程的各个步骤。介体的主要功能是将来自与增强子区域结合的转录激活因子的信号转导至转录机制,后者在启动子处组装为预起始复合物(PIC),以控制转录起始。使用结构生物学方法和功能基因组学对Mediator进行的近期功能研究揭示了对Mediator活性及其在转录起始过程中的调控的新见解,包括Mediator如何被招募到转录调控区域,以及它如何与PIC成分相互作用和协作以协助进行介导。 PIC组件。还通过显示介体与核孔的连接以及将介体与核空间中基因定位的调节联系起来,揭示了介体在基因表达控制中的新作用。介体亚基与疾病之间的明确联系也鼓励研究探索靶向这种复合物作为癌症和真菌感染的潜在治疗方法。包括调解员如何被招募到转录调控区,以及它如何与PIC组件相互作用和合作以协助PIC组装。还通过显示介体与核孔的连接以及将介体与核空间中基因定位的调节联系起来,揭示了介体在基因表达控制中的新作用。介体亚基与疾病之间的明确联系也鼓励研究探索靶向这种复合物作为癌症和真菌感染的潜在治疗方法。包括调解员如何被招募到转录调控区,以及它如何与PIC组件相互作用和合作以协助PIC组装。还通过显示介体与核孔的连接以及将介体与核空间中基因定位的调节联系起来,揭示了介体在基因表达控制中的新作用。介体亚基与疾病之间的明确联系也鼓励研究探索靶向这种复合物作为癌症和真菌感染的潜在治疗方法。

更新日期:2017-12-06
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