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Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback

A fundamental trade-off between rapid response and optimal expression of genes below cytotoxic levels exists for many signaling circuits, particularly for positively autoregulated systems with an inherent response delay. Here, we describe a regulatory scheme in the E. coli PhoB-PhoR two-component sy...

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Detalles Bibliográficos
Autores principales: Gao, Rong, Stock, Ann M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194859/
https://www.ncbi.nlm.nih.gov/pubmed/30208328
http://dx.doi.org/10.1016/j.celrep.2018.08.023
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author Gao, Rong
Stock, Ann M.
author_facet Gao, Rong
Stock, Ann M.
author_sort Gao, Rong
collection PubMed
description A fundamental trade-off between rapid response and optimal expression of genes below cytotoxic levels exists for many signaling circuits, particularly for positively autoregulated systems with an inherent response delay. Here, we describe a regulatory scheme in the E. coli PhoB-PhoR two-component system, which overcomes the cost of positive feedback and achieves both fast and optimal steadystate response for maximal fitness across different environments. Quantitation of the cellular activities enables accurate modeling of the response dynamics to describe how requirements for optimal protein concentrations place limits on response speed. An observed fast response that exceeds the limit led to the prediction and discovery of a coupled negative autoregulation, which allows fast gene expression without increasing steady-state levels. We demonstrate the fitness advantages for the coupled feedbacks in both dynamic and stable environments. Such regulatory schemes offer great flexibility for accurate control of gene expression levels and dynamics upon environmental changes.
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spelling pubmed-61948592018-10-19 Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback Gao, Rong Stock, Ann M. Cell Rep Article A fundamental trade-off between rapid response and optimal expression of genes below cytotoxic levels exists for many signaling circuits, particularly for positively autoregulated systems with an inherent response delay. Here, we describe a regulatory scheme in the E. coli PhoB-PhoR two-component system, which overcomes the cost of positive feedback and achieves both fast and optimal steadystate response for maximal fitness across different environments. Quantitation of the cellular activities enables accurate modeling of the response dynamics to describe how requirements for optimal protein concentrations place limits on response speed. An observed fast response that exceeds the limit led to the prediction and discovery of a coupled negative autoregulation, which allows fast gene expression without increasing steady-state levels. We demonstrate the fitness advantages for the coupled feedbacks in both dynamic and stable environments. Such regulatory schemes offer great flexibility for accurate control of gene expression levels and dynamics upon environmental changes. 2018-09-11 /pmc/articles/PMC6194859/ /pubmed/30208328 http://dx.doi.org/10.1016/j.celrep.2018.08.023 Text en This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Rong
Stock, Ann M.
Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
title Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
title_full Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
title_fullStr Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
title_full_unstemmed Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
title_short Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
title_sort overcoming the cost of positive autoregulation by accelerating the response with a coupled negative feedback
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194859/
https://www.ncbi.nlm.nih.gov/pubmed/30208328
http://dx.doi.org/10.1016/j.celrep.2018.08.023
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