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从RNA聚合酶与DNA结合的平衡模型洞察转录调控和σ因子竞争

Insights into transcriptional regulation and sigma competition from an equilibrium model of RNA polymerase binding to DNA.

作者信息

Grigorova Irina L, Phleger Naum J, Mutalik Vivek K, Gross Carol A

机构信息

Graduate Group in Biophysics and Department of Microbiology, University of California-San Francisco, 600 16th Street, Genentech Hall, Box 2200, San Francisco, CA 94143, USA.

出版信息

Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5332-7. doi: 10.1073/pnas.0600828103. Epub 2006 Mar 27.

Abstract

To explore scenarios that permit transcription regulation by activator recruitment of RNA polymerase and sigma competition in vivo, we used an equilibrium model of RNA polymerase binding to DNA constrained by the values of total RNA polymerase (E) and sigma(70) per cell measured in this work. Our numbers of E and sigma(70) per cell, which are consistent with most of the primary data in the literature, suggest that in vivo (i) only a minor fraction of RNA polymerase (<20%) is involved in elongation and (ii) sigma(70) is in excess of total E. Modeling the partitioning of RNA polymerase between promoters, nonspecific DNA binding sites, and the cytoplasm suggested that even weak promoters will be saturated with Esigma(70) in vivo unless nonspecific DNA binding by Esigma(70) is rather significant. In addition, the model predicted that sigmas compete for binding to E only when their total number exceeds the total amount of RNA polymerase (excluding that involved in elongation) and that weak promoters will be preferentially subjected to sigma competition.

摘要

为了探索在体内通过激活剂招募RNA聚合酶和σ因子竞争来实现转录调控的情况,我们使用了一个RNA聚合酶与DNA结合的平衡模型,该模型受这项工作中测得的每个细胞中总RNA聚合酶(E)和σ⁷⁰的值的限制。我们测得的每个细胞中E和σ⁷⁰的数量与文献中的大多数原始数据一致,这表明在体内:(i)只有一小部分RNA聚合酶(<20%)参与延伸;(ii)σ⁷⁰的数量超过了总E的数量。对RNA聚合酶在启动子、非特异性DNA结合位点和细胞质之间的分配进行建模表明,除非Eσ⁷⁰与非特异性DNA的结合相当显著,否则即使是弱启动子在体内也会被Eσ⁷⁰饱和。此外,该模型预测,只有当σ因子的总数超过RNA聚合酶的总量(不包括参与延伸的部分)时,它们才会竞争与E的结合,并且弱启动子将优先受到σ因子竞争的影响。

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