On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks
The temporal dynamics of the concentrations of several proteins are tightly regulated, particularly for critical nodes in biological networks such as transcription factors. An important mechanism to control transcription factor levels is through autoregulatory feedback loops where the protein can bi...
| Autores principales: | , |
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| Otros Autores: | |
| Formato: | Artículo |
| Lenguaje: | en_US |
| Publicado: |
Elsevier
2014
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| Acceso en línea: | http://hdl.handle.net/1721.1/90264 |
| _version_ | 1826194952964538368 |
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| author | Murugan, Rajamanickam Kreiman, Gabriel |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT Murugan, Rajamanickam Kreiman, Gabriel |
| author_sort | Murugan, Rajamanickam |
| collection | MIT |
| description | The temporal dynamics of the concentrations of several proteins are tightly regulated, particularly for critical nodes in biological networks such as transcription factors. An important mechanism to control transcription factor levels is through autoregulatory feedback loops where the protein can bind its own promoter. Here we use theoretical tools and computational simulations to further our understanding of transcription-factor autoregulatory loops. We show that the stochastic dynamics of feedback and mRNA synthesis can significantly influence the speed of response of autoregulatory genetic networks toward external stimuli. The fluctuations in the response-times associated with the accumulation of the transcription factor in the presence of negative or positive autoregulation can be minimized by confining the ratio of mRNA/protein lifetimes within 1:10. This predicted range of mRNA/protein lifetime agrees with ranges observed empirically in prokaryotes and eukaryotes. The theory can quantitatively and systematically account for the influence of regulatory element binding and unbinding dynamics on the transcription-factor concentration rise-times. The simulation results are robust against changes in several system parameters of the gene expression machinery. |
| first_indexed | 2024-09-23T10:04:43Z |
| format | Article |
| id | mit-1721.1/90264 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:04:43Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/902642022-09-26T15:32:41Z On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks Murugan, Rajamanickam Kreiman, Gabriel McGovern Institute for Brain Research at MIT Kreiman, Gabriel The temporal dynamics of the concentrations of several proteins are tightly regulated, particularly for critical nodes in biological networks such as transcription factors. An important mechanism to control transcription factor levels is through autoregulatory feedback loops where the protein can bind its own promoter. Here we use theoretical tools and computational simulations to further our understanding of transcription-factor autoregulatory loops. We show that the stochastic dynamics of feedback and mRNA synthesis can significantly influence the speed of response of autoregulatory genetic networks toward external stimuli. The fluctuations in the response-times associated with the accumulation of the transcription factor in the presence of negative or positive autoregulation can be minimized by confining the ratio of mRNA/protein lifetimes within 1:10. This predicted range of mRNA/protein lifetime agrees with ranges observed empirically in prokaryotes and eukaryotes. The theory can quantitatively and systematically account for the influence of regulatory element binding and unbinding dynamics on the transcription-factor concentration rise-times. The simulation results are robust against changes in several system parameters of the gene expression machinery. National Science Foundation (U.S.) National Institutes of Health (U.S.) 2014-09-22T17:55:18Z 2014-09-22T17:55:18Z 2011-09 2011-03 Article http://purl.org/eprint/type/JournalArticle 00063495 1542-0086 http://hdl.handle.net/1721.1/90264 Murugan, Rajamanickam, and Gabriel Kreiman. “On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks.” Biophysical Journal 101, no. 6 (September 2011): 1297–1306. © Biophysical Society en_US http://dx.doi.org/10.1016/j.bpj.2011.08.005 Biophysical Journal Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Murugan, Rajamanickam Kreiman, Gabriel On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks |
| title | On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks |
| title_full | On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks |
| title_fullStr | On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks |
| title_full_unstemmed | On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks |
| title_short | On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks |
| title_sort | on the minimization of fluctuations in the response times of autoregulatory gene networks |
| url | http://hdl.handle.net/1721.1/90264 |
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