转录前起始复合物的组装和启动子识别机制  

Assembly and promoter recognition mechanisms of pretranscriptional initiation complexes

作　　者：陈曦子 徐彦辉 CHEN Xizi;XU Yanhui(Fudan University Shanghai Cancer Center/Institutes of Biomedical Sciences,Shanghai Medical College of Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学上海医学院,复旦大学附属肿瘤医院/生物医学研究院,上海200032

出　　处：《自然杂志》2023年第2期79-88,共10页Chinese Journal of Nature

摘　　要：基因转录作为中心法则的关键环节,将遗传信息由DNA传递至RNA,从而指导蛋白质的合成,是生物体最重要的生命活动之一。转录起始过程发生在几万种不同基因的高度多样化的启动子区,启动子区转录前起始复合物(PIC)的装配是转录起始的关键步骤,受到极其复杂的调控,是基因表达调控的核心。数十年来,大量基于TBP-TATA框体系开展的PIC结构和功能研究逐步揭示了基于TBP的PIC在TATA框启动子上的组装机制。近年来,研究显示,人类超过85%基因启动子不含有TATA框,并且几乎所有的基因转录过程都需要TFIID参与,且功能并不能够被TBP所替代。近期,基于TFIID的不同组装阶段的PIC结构和包含+1核小体的复合物结构的研究突破,首次系统地展示了PIC识别不同类型启动子及其在染色质上组装的分子过程,为后续研究基因表达调控提供了理论基础。As the key step of the genetic central dogma,transcription generates RNA using DNA as template to control differential gene expression.The transcription initiation occurs in highly diverse promoter regions of tens of thousands of different genes.The preinitiation complex(PIC)assembly on core promoter is a key step of eukaryotic transcription initiation and requires precise regulation.Previous structural studies focused on PIC assembled on TATA box promoters with TFIID replaced by its subunit,TATA box-binding protein(TBP).However,the TFIID complex is essential for PIC assembly for almost all Pol II-mediated transcription,especially on the TATA-less promoters,which account for more than 85%of core promoters of human coding genes.The functions of TFIID could not be replaced by TBP.The recent breakthrough in structure determination of TFIID-based PIC complexes in different assembly stages and in complex of the+1 nucleosome revealed mechanistic insights into PIC assembly on core promotes and in the context of chromatin,providing a framework for further investigation of transcription initiation.

关 键 词：转录前起始复合物 转录起始 转录调控 

分 类 号：Q75[生物学—分子生物学]