Synthetic mammalian transgene negative autoregulation
Abstract Biological 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 cel...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2013-06-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2013.27 |
| _version_ | 1826990464817954816 |
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| author | Vinay Shimoga Jacob T White Yi Li Eduardo Sontag Leonidas Bleris |
| author_facet | Vinay Shimoga Jacob T White Yi Li Eduardo Sontag Leonidas Bleris |
| author_sort | Vinay Shimoga |
| collection | DOAJ |
| description | Abstract Biological 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. |
| first_indexed | 2024-03-07T16:37:45Z |
| format | Article |
| id | doaj.art-bb91144f3cc34b1a857ea9220e34ccea |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2025-02-18T08:20:59Z |
| publishDate | 2013-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-bb91144f3cc34b1a857ea9220e34ccea2024-11-03T12:56:14ZengSpringer NatureMolecular Systems Biology1744-42922013-06-01911710.1038/msb.2013.27Synthetic mammalian transgene negative autoregulationVinay Shimoga0Jacob T White1Yi Li2Eduardo Sontag3Leonidas Bleris4Bioengineering Department, The University of Texas at DallasBioengineering Department, The University of Texas at DallasBioengineering Department, The University of Texas at DallasDepartment of Mathematics, Rutgers UniversityBioengineering Department, The University of Texas at DallasAbstract Biological 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.https://doi.org/10.1038/msb.2013.27cellular noisehuman cellsnegative feedbacktransgenes |
| spellingShingle | Vinay Shimoga Jacob T White Yi Li Eduardo Sontag Leonidas Bleris Synthetic mammalian transgene negative autoregulation Molecular Systems Biology cellular noise human cells negative feedback transgenes |
| title | Synthetic mammalian transgene negative autoregulation |
| title_full | Synthetic mammalian transgene negative autoregulation |
| title_fullStr | Synthetic mammalian transgene negative autoregulation |
| title_full_unstemmed | Synthetic mammalian transgene negative autoregulation |
| title_short | Synthetic mammalian transgene negative autoregulation |
| title_sort | synthetic mammalian transgene negative autoregulation |
| topic | cellular noise human cells negative feedback transgenes |
| url | https://doi.org/10.1038/msb.2013.27 |
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