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Noise in transcription negative feedback loops: simulation and experimental analysis

Negative feedback loops have been invoked as a way to control and decrease transcriptional noise. Here, we have built three circuits to test the effect of negative feedback loops on transcriptional noise of an autoregulated gene encoding a transcription factor (TF) and a downstream gene (DG), regula...

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Autores principales: Dublanche, Yann, Michalodimitrakis, Konstantinos, Kümmerer, Nico, Foglierini, Mathilde, Serrano, Luis
Formato: Texto
Lenguaje:English
Publicado: 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681513/
https://www.ncbi.nlm.nih.gov/pubmed/16883354
http://dx.doi.org/10.1038/msb4100081
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author Dublanche, Yann
Michalodimitrakis, Konstantinos
Kümmerer, Nico
Foglierini, Mathilde
Serrano, Luis
author_facet Dublanche, Yann
Michalodimitrakis, Konstantinos
Kümmerer, Nico
Foglierini, Mathilde
Serrano, Luis
author_sort Dublanche, Yann
collection PubMed
description Negative feedback loops have been invoked as a way to control and decrease transcriptional noise. Here, we have built three circuits to test the effect of negative feedback loops on transcriptional noise of an autoregulated gene encoding a transcription factor (TF) and a downstream gene (DG), regulated by this TF. Experimental analysis shows that self-repression decreases noise compared to expression from a non-regulated promoter. Interestingly enough, we find that noise minimization by negative feedback loop is optimal within a range of repression strength. Repression values outside this range result in noise increase producing a U-shaped behaviour. This behaviour is the result of external noise probably arising from plasmid fluctuations as shown by simulation of the network. Regarding the target gene of a self-repressed TF (sTF), we find a strong decrease of noise when repression by the sTF is strong and a higher degree of noise anti-correlation between sTF and its target. Simulations of the circuits indicate that the main source of noise in these circuits could come from plasmid variation and therefore that negative feedback loops play an important role in suppressing both external and internal noise. An important observation is that DG expression without negative feedback exhibits bimodality at intermediate TF repression values. This bimodal behaviour seems to be the result of external noise as it can only be found in those simulations that include plasmid variation.
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spelling pubmed-16815132007-01-25 Noise in transcription negative feedback loops: simulation and experimental analysis Dublanche, Yann Michalodimitrakis, Konstantinos Kümmerer, Nico Foglierini, Mathilde Serrano, Luis Mol Syst Biol Article Negative feedback loops have been invoked as a way to control and decrease transcriptional noise. Here, we have built three circuits to test the effect of negative feedback loops on transcriptional noise of an autoregulated gene encoding a transcription factor (TF) and a downstream gene (DG), regulated by this TF. Experimental analysis shows that self-repression decreases noise compared to expression from a non-regulated promoter. Interestingly enough, we find that noise minimization by negative feedback loop is optimal within a range of repression strength. Repression values outside this range result in noise increase producing a U-shaped behaviour. This behaviour is the result of external noise probably arising from plasmid fluctuations as shown by simulation of the network. Regarding the target gene of a self-repressed TF (sTF), we find a strong decrease of noise when repression by the sTF is strong and a higher degree of noise anti-correlation between sTF and its target. Simulations of the circuits indicate that the main source of noise in these circuits could come from plasmid variation and therefore that negative feedback loops play an important role in suppressing both external and internal noise. An important observation is that DG expression without negative feedback exhibits bimodality at intermediate TF repression values. This bimodal behaviour seems to be the result of external noise as it can only be found in those simulations that include plasmid variation. 2006-08-01 /pmc/articles/PMC1681513/ /pubmed/16883354 http://dx.doi.org/10.1038/msb4100081 Text en Copyright © 2006, EMBO and Nature Publishing Group
spellingShingle Article
Dublanche, Yann
Michalodimitrakis, Konstantinos
Kümmerer, Nico
Foglierini, Mathilde
Serrano, Luis
Noise in transcription negative feedback loops: simulation and experimental analysis
title Noise in transcription negative feedback loops: simulation and experimental analysis
title_full Noise in transcription negative feedback loops: simulation and experimental analysis
title_fullStr Noise in transcription negative feedback loops: simulation and experimental analysis
title_full_unstemmed Noise in transcription negative feedback loops: simulation and experimental analysis
title_short Noise in transcription negative feedback loops: simulation and experimental analysis
title_sort noise in transcription negative feedback loops: simulation and experimental analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681513/
https://www.ncbi.nlm.nih.gov/pubmed/16883354
http://dx.doi.org/10.1038/msb4100081
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