Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations.

IF 1.2 Q3 PHYSICS, MULTIDISCIPLINARY Papers in Physics Pub Date : 2014-12-02 eCollection Date: 2014-01-01 DOI:10.4279/PIP.060012
Ivan M Lengyel, Daniele Soroldoni, Andrew C Oates, Luis G Morelli
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Abstract

We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.

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非合作转录因子结合引起的非线性增强了负反馈,促进了遗传振荡。
我们研究了基因振荡器启动子中多个结合位点的影响。我们评估了具有多个结合位点的启动子在缺乏合作结合的情况下的调节功能,并考虑了结合抑制子数量如何影响转录速率的不同假设。所得到的调节函数的有效希尔指数显示,随着结合位点的数量,反馈的非线性增加。我们确定了使反馈非线性最大化的最优配置。我们使用生化振荡器的通用模型来表明,这种增加的非线性反映在增强的振荡中,在更宽的振荡范围内具有更大的振幅。虽然这项研究的动机是斑马鱼分割时钟的遗传振荡,但我们的发现可能揭示了基因调控的一般原理。
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来源期刊
Papers in Physics
Papers in Physics PHYSICS, MULTIDISCIPLINARY-
CiteScore
1.90
自引率
0.00%
发文量
13
期刊介绍: Papers in Physics publishes original research in all areas of physics and its interface with other subjects. The scope includes, but is not limited to, physics of particles and fields, condensed matter, relativity and gravitation, nuclear physics, physics of fluids, biophysics, econophysics, chemical physics, statistical mechanics, soft condensed matter, materials science, mathematical physics and general physics. Contributions in the areas of foundations of physics, history of physics and physics education are not considered for publication. Articles published in Papers in Physics contain substantial new results and ideas that advance the state of physics in a non-trivial way. Articles are strictly reviewed by specialists prior to publication. Papers in Physics highlights outstanding articles published in the journal through the Editors'' choice section. Papers in Physics offers two distinct editorial treatments to articles from which authors can choose. In Traditional Review, manuscripts are submitted to anonymous reviewers seeking constructive criticism and editors make a decision on whether publication is appropriate. In Open Review, manuscripts are sent to reviewers. If the paper is considered original and technically sound, the article, the reviewer''s comments and the author''s reply are published alongside the names of all involved. This way, Papers in Physics promotes the open discussion of controversies among specialists that are of help to the reader and to the transparency of the editorial process. Moreover, our reviewers receive their due recognition by publishing a recorded citable report. Papers in Physics publishes Commentaries from the reviewer(s) if major disagreements remain after exchange with the authors or if a different insight proposed is considered valuable for the readers.
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