Core promoter sequence in yeast is a major determinant of expression level.

Core promoter sequence in yeast is a major determinant of expression level.
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DOI:
10.1101/gr.188193.114
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发表时间:
2015-07
期刊:
影响因子:
7
通讯作者:
Segal E
Segal E
中科院分区:
生物学1区
文献类型:
--
作者:
Lubliner S;Regev I;Lotan-Pompan M;Edelheit S;Weinberger A;Segal E

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核心启动子是RNA聚合酶被募集到的调控序列,并且在其中其起作用以启动转录。在这里,我们提出了第一个全面的研究酵母核心启动子,提供大规模并行测量的核心启动子的活性和TSS的位置和相对使用数以千计的本地和设计的序列。我们发现核心启动子活性与整个启动子的活性高度相关,并且不同核心启动子区域中的序列变异以可预测的方式显著调节其活性。我们还表明,位置,方向和侧翼碱基严重影响TATA元件的功能,在高活性的核心启动子的转录起始集中在一个狭窄的区域内,聚(dA:dT)的方向有一个功能性的后果在3 '端的启动子,并在整个酵母物种的正交核心启动子具有保守的活动。我们的研究结果表明核心启动子在基因调控定量研究中的重要性。
The core promoter is the regulatory sequence to which RNA polymerase is recruited and where it acts to initiate transcription. Here, we present the first comprehensive study of yeast core promoters, providing massively parallel measurements of core promoter activity and of TSS locations and relative usage for thousands of native and designed sequences. We found core promoter activity to be highly correlated to the activity of the entire promoter and that sequence variation in different core promoter regions substantially tunes its activity in a predictable way. We also show that location, orientation, and flanking bases critically affect TATA element function, that transcription initiation in highly active core promoters is focused within a narrow region, that poly(dA:dT) orientation has a functional consequence at the 3′ end of promoters, and that orthologous core promoters across yeast species have conserved activities. Our results demonstrate the importance of core promoters in the quantitative study of gene regulation.
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