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

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...

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Main Authors: Iván M. Lengyel, Daniele Soroldoni, Andrew C. Oates, Luis G. Morelli
Format: Article
Language:English
Published: Papers in Physics 2014-11-01
Series:Papers in Physics
Subjects:
Online Access:http://www.papersinphysics.org/index.php/papersinphysics/article/view/206/pdf206
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author Iván M. Lengyel
Daniele Soroldoni
Andrew C. Oates
Luis G. Morelli
author_facet Iván M. Lengyel
Daniele Soroldoni
Andrew C. Oates
Luis G. Morelli
author_sort Iván M. Lengyel
collection DOAJ
description 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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spelling doaj.art-f717b7e2b341476f8f067bbd2a53b79f2022-12-22T03:18:26ZengPapers in PhysicsPapers in Physics1852-42491852-42492014-11-016006001210.4279/PIP.060012Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillationsIván M. LengyelDaniele SoroldoniAndrew C. OatesLuis G. MorelliWe 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.http://www.papersinphysics.org/index.php/papersinphysics/article/view/206/pdf206genetic oscillationsnegative feedbackcooperativity
spellingShingle Iván M. Lengyel
Daniele Soroldoni
Andrew C. Oates
Luis G. Morelli
Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
Papers in Physics
genetic oscillations
negative feedback
cooperativity
title Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_full Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_fullStr Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_full_unstemmed Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_short Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_sort nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
topic genetic oscillations
negative feedback
cooperativity
url http://www.papersinphysics.org/index.php/papersinphysics/article/view/206/pdf206
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AT andrewcoates nonlinearityarisingfromnoncooperativetranscriptionfactorbindingenhancesnegativefeedbackandpromotesgeneticoscillations
AT luisgmorelli nonlinearityarisingfromnoncooperativetranscriptionfactorbindingenhancesnegativefeedbackandpromotesgeneticoscillations