Show simple item record

dc.contributor.authorMurphy, Kevin F.en_US
dc.contributor.authorAdams, Rhys M.en_US
dc.contributor.authorWang, Xiaoen_US
dc.contributor.authorBalázsi, Gáboren_US
dc.contributor.authorCollins, James J.en_US
dc.date.accessioned2012-01-11T00:40:40Z
dc.date.available2012-01-11T00:40:40Z
dc.date.copyright2010en_US
dc.date.issued2010-03-08en_US
dc.identifier.citationMurphy, 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.issn1362-4962en_US
dc.identifier.urihttp://hdl.handle.net/2144/3034
dc.description.abstractSynthetic 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.sponsorshipNational 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.isoenen_US
dc.publisherOxford University Pressen_US
dc.rightsCopyright Murphy, Kevin F., Rhys M. Adams, Xiao Wang, Gábor Balászi, James J. Collins 2010. Published by Oxford University Press.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/2.5en_US
dc.titleTuning and Controlling Gene Expression Noise in Synthetic Gene Networksen_US
dc.typearticleen_US
dc.identifier.doi10.1093/nar/gkq091en_US
dc.identifier.pubmedid20211838en_US
dc.identifier.pmcid2860118en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

Copyright Murphy, Kevin F., Rhys M. Adams, Xiao Wang, Gábor Balászi, James J. Collins 2010. Published by Oxford University Press.
Except where otherwise noted, this item's license is described as Copyright Murphy, Kevin F., Rhys M. Adams, Xiao Wang, Gábor Balászi, James J. Collins 2010. Published by Oxford University Press.