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SAGA的结构和TBP在基因启动子上的聚集机理
2020-01-28 22:51

SAGA的结构和TBP在基因启动子上的聚集机理,这一成果由法国Equipe labellisée抗癌联盟Adam Ben-Shem、Patrick Schultz等研究人员合作完成。2020年1月22日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员报道了结合TATA盒结合蛋白(TBP)的酵母SAGA的结构。该复合物的核心分辨率为3.5Å(0.143傅里叶壳相关性)。该结构揭示了相互作用的复杂网络,这些相互作用协调了SAGA的不同功能域,并解析了SAGA核心组蛋白折叠结构域的八聚体。这种变形的八聚体大大偏离了核小体中的对称类似物,并经过精确调节以建立TBP的外围位点,这些位点的空间位阻抑制了错误DNA的结合。互补的生化分析指出,TBP从SAGA传递和释放的机制需要转录因子IIA,并且其效率与DNA对TBP的亲和力有关。研究人员提供了了解TBP到基因启动子的具体特有传递以及SAGA在调控基因表达中多种作用的基础。

据介绍,SAGA(Spt–Ada–Gcn5–乙酰基转移酶)是一个19亚基复合物,可通过两个染色质修饰酶模块刺激转录,并通过TBP来聚合DNA上的预起始复合物,这是在蛋白质编码基因的表达中的一个关键事件。

附:英文原文

Title: Structure of SAGA and mechanism of TBP deposition on gene promoters

Author: Gabor Papai, Alexandre Frechard, Olga Kolesnikova, Corinne Crucifix, Patrick Schultz, Adam Ben-Shem

Issue&Volume: 2020-01-22

Abstract: SAGA (Spt–Ada–Gcn5–acetyltransferase) is a 19-subunit complex that stimulates transcription via two chromatin-modifying enzymatic modules and by delivering the TATA box binding protein (TBP) to nucleate the pre-initiation complex on DNA, a pivotal event in the expression of protein-encoding genes1. Here we present the structure of yeast SAGA with bound TBP. The core of the complex is resolved at 3.5 resolution (0.143 Fourier shell correlation). The structure reveals the intricate network of interactions that coordinate the different functional domains of SAGA and resolves an octamer of histone-fold domains at the core of SAGA. This deformed octamer deviates considerably from the symmetrical analogue in the nucleosome and is precisely tuned to establish a peripheral site for TBP, where steric hindrance represses binding of spurious DNA. Complementary biochemical analysis points to a mechanism for TBP delivery and release from SAGA that requires transcription factor IIA and whose efficiency correlates with the affinity of DNA to TBP. We provide the foundations for understanding the specific delivery of TBP to gene promoters and the multiple roles of SAGA in regulating gene expression.

DOI: 10.1038/s41586-020-1944-2

Source: https://www.nature.com/articles/s41586-020-1944-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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