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dc.contributor.authorShimoga, Vinayen_US
dc.contributor.authorWhite, Jacob T.en_US
dc.contributor.authorLi, Yien_US
dc.contributor.authorSontag, Eduardoen_US
dc.contributor.authorBleris, Leonidasen_US
dc.date.accessioned2014-08-22T19:11:38Z
dc.date.available2014-08-22T19:11:38Z
dc.date.created2013-06-04
dc.date.issued2013-06-04en_US
dc.identifier.citationShimoga, Vinay, Jacob T. White, Yi Li, Eduardo Sontag, et al. 2013. "Synthetic mammalian transgene negative autoregulation." 9(670): 1-7.en_US
dc.identifier.issn1744-4292en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/3916
dc.description.abstractBiological networks contain overrepresented small-scale topologies, typically called motifs. A frequently appearing motif is the transcriptional negative-feedback loop, where a gene product represses its own transcription. Here, using synthetic circuits stably integrated in human kidney cells, we study the effect of negative-feedback regulation on cell-wide (extrinsic) and gene-specific (intrinsic) sources of uncertainty. We develop a theoretical approach to extract the two noise components from experiments and show that negative feedback results in significant total noise reduction by reducing extrinsic noise while marginally increasing intrinsic noise. We compare the results to simple negative regulation, where a constitutively transcribed transcription factor represses a reporter protein. We observe that the control architecture also reduces the extrinsic noise but results in substantially higher intrinsic fluctuations. We conclude that negative feedback is the most efficient way to mitigate the effects of extrinsic fluctuations by a sole regulatory wiring.;en_US
dc.description.sponsorshipNIH grant 1R15GM096271; Texas Analog Center of Excellence (TxACE) grant P1209; NSF award CBET-110552en_US
dc.relation.urihttp://dx.doi.org/10.1038/msb.2013.27en_US
dc.rightsCC BY 3.0 (Attribution)en_US
dc.rights©2013 EMBO and Macmillan Publishers Limiteden_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.subjectSynthetic biologyen_US
dc.subjectTransgenesen_US
dc.subjectNoiseen_US
dc.subjectProteinsen_US
dc.titleSynthetic Mammalian Transgene Negative Autoregulationen_US
dc.type.genrearticleen_US
dc.source.journalMolecular Systems Biologyen_US
dc.identifier.volume9en_US
dc.identifier.issue670en_US
dc.contributor.ISNI0000 0001 2535 9739 (Bleris, L)
dc.contributor.LCNA2012076942‏ (Bleris, L)


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