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Tuning and controlling gene expression noise in synthetic gene networks
Synthetic gene networks can be used to control gene expression and cellular phenotypes in a variety of applications. In many instances, however, such networks can behave unreliably due to gene expression noise. Accordingly, there is a need to develop systematic means to tune gene expression noise, s...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860118/ https://www.ncbi.nlm.nih.gov/pubmed/20211838 http://dx.doi.org/10.1093/nar/gkq091 |
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author | Murphy, Kevin F. Adams, Rhys M. Wang, Xiao Balázsi, Gábor Collins, James J. |
author_facet | Murphy, Kevin F. Adams, Rhys M. Wang, Xiao Balázsi, Gábor Collins, James J. |
author_sort | Murphy, Kevin F. |
collection | PubMed |
description | Synthetic gene networks can be used to control gene expression and cellular phenotypes in a variety of applications. In many instances, however, such networks can behave unreliably due to gene expression noise. Accordingly, there is a need to develop systematic means to tune gene expression noise, so that it can be suppressed in some cases and harnessed in others, e.g. in cellular differentiation to create population-wide heterogeneity. Here, we present a method for controlling noise in synthetic eukaryotic gene expression systems, utilizing reduction of noise levels by TATA box mutations and noise propagation in transcriptional cascades. Specifically, we introduce TATA box mutations into promoters driving TetR expression and show that these mutations can be used to effectively tune the noise of a target gene while decoupling it from the mean, with negligible effects on the dynamic range and basal expression. We apply mathematical and computational modeling to explain the experimentally observed effects of TATA box mutations. This work, which highlights some important aspects of noise propagation in gene regulatory cascades, has practical implications for implementing gene expression control in synthetic gene networks. |
format | Text |
id | pubmed-2860118 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28601182010-04-27 Tuning and controlling gene expression noise in synthetic gene networks Murphy, Kevin F. Adams, Rhys M. Wang, Xiao Balázsi, Gábor Collins, James J. Nucleic Acids Res Synthetic Biology and Chemistry Synthetic gene networks can be used to control gene expression and cellular phenotypes in a variety of applications. In many instances, however, such networks can behave unreliably due to gene expression noise. Accordingly, there is a need to develop systematic means to tune gene expression noise, so that it can be suppressed in some cases and harnessed in others, e.g. in cellular differentiation to create population-wide heterogeneity. Here, we present a method for controlling noise in synthetic eukaryotic gene expression systems, utilizing reduction of noise levels by TATA box mutations and noise propagation in transcriptional cascades. Specifically, we introduce TATA box mutations into promoters driving TetR expression and show that these mutations can be used to effectively tune the noise of a target gene while decoupling it from the mean, with negligible effects on the dynamic range and basal expression. We apply mathematical and computational modeling to explain the experimentally observed effects of TATA box mutations. This work, which highlights some important aspects of noise propagation in gene regulatory cascades, has practical implications for implementing gene expression control in synthetic gene networks. Oxford University Press 2010-05 2010-03-08 /pmc/articles/PMC2860118/ /pubmed/20211838 http://dx.doi.org/10.1093/nar/gkq091 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Synthetic Biology and Chemistry Murphy, Kevin F. Adams, Rhys M. Wang, Xiao Balázsi, Gábor Collins, James J. Tuning and controlling gene expression noise in synthetic gene networks |
title | Tuning and controlling gene expression noise in synthetic gene networks |
title_full | Tuning and controlling gene expression noise in synthetic gene networks |
title_fullStr | Tuning and controlling gene expression noise in synthetic gene networks |
title_full_unstemmed | Tuning and controlling gene expression noise in synthetic gene networks |
title_short | Tuning and controlling gene expression noise in synthetic gene networks |
title_sort | tuning and controlling gene expression noise in synthetic gene networks |
topic | Synthetic Biology and Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860118/ https://www.ncbi.nlm.nih.gov/pubmed/20211838 http://dx.doi.org/10.1093/nar/gkq091 |
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