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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Language: | English |
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Papers in Physics
2014-11-01
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Series: | Papers in Physics |
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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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format | Article |
id | doaj.art-f717b7e2b341476f8f067bbd2a53b79f |
institution | Directory Open Access Journal |
issn | 1852-4249 1852-4249 |
language | English |
last_indexed | 2024-04-12T20:05:09Z |
publishDate | 2014-11-01 |
publisher | Papers in Physics |
record_format | Article |
series | Papers in Physics |
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 |
work_keys_str_mv | AT ivanmlengyel nonlinearityarisingfromnoncooperativetranscriptionfactorbindingenhancesnegativefeedbackandpromotesgeneticoscillations AT danielesoroldoni nonlinearityarisingfromnoncooperativetranscriptionfactorbindingenhancesnegativefeedbackandpromotesgeneticoscillations AT andrewcoates nonlinearityarisingfromnoncooperativetranscriptionfactorbindingenhancesnegativefeedbackandpromotesgeneticoscillations AT luisgmorelli nonlinearityarisingfromnoncooperativetranscriptionfactorbindingenhancesnegativefeedbackandpromotesgeneticoscillations |