Tuning and Controlling Gene Expression Noise in Synthetic Gene Networks

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dc.contributor.author Murphy, Kevin F. en_US
dc.contributor.author Adams, Rhys M. en_US
dc.contributor.author Wang, Xiao en_US
dc.contributor.author Balázsi, Gábor en_US
dc.contributor.author Collins, James J. en_US
dc.date.accessioned 2012-01-11T00:40:40Z
dc.date.available 2012-01-11T00:40:40Z
dc.date.copyright 2010 en_US
dc.date.issued 2010-03-08 en_US
dc.identifier.citation Murphy, Kevin F., Rhys M. Adams, Xiao Wang, Gábor Balászi, James J. Collins. "Tuning and controlling gene expression noise in synthetic gene networks" Nucleic Acids Research 38(8): 2712-2726. (2010) en_US
dc.identifier.issn 1362-4962 en_US
dc.identifier.uri http://hdl.handle.net/2144/3034
dc.description.abstract 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. en_US
dc.description.sponsorship National Institutes of Health Director's Pioneer Award Program (DP1 OD00344); the National Institutes of Health Director's New Innovator Award Program (1DP2 OD006481-01); the National Science Foundation Frontiers in Integrative Biological Research Program; Howard Hughes Medical Institute; The University of Texas M. D. Anderson Cancer Center. en_US
dc.language.iso en en_US
dc.publisher Oxford University Press en_US
dc.rights Copyright Murphy, Kevin F., Rhys M. Adams, Xiao Wang, Gábor Balászi, James J. Collins 2010. Published by Oxford University Press. en_US
dc.rights.uri http://creativecommons.org/licenses/by-nc/2.5 en_US
dc.title Tuning and Controlling Gene Expression Noise in Synthetic Gene Networks en_US
dc.type article en_US
dc.identifier.doi 10.1093/nar/gkq091 en_US
dc.identifier.pubmedid 20211838 en_US
dc.identifier.pmcid 2860118 en_US

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