Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template
Natural and synthetic biological networks must function reliably in the face of fluctuating stoichiometry of their molecular components. These fluctuations are caused in part by changes in relative expression efficiency and the DNA template amount of the network-coding genes. Gene product levels cou...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/77595 |
| _version_ | 1826205166624309248 |
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| author | Bleris, Leonidas Xie, Zhen Glass, David Adadey, Asa Sontag, Eduardo Benenson, Yaakov |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Bleris, Leonidas Xie, Zhen Glass, David Adadey, Asa Sontag, Eduardo Benenson, Yaakov |
| author_sort | Bleris, Leonidas |
| collection | MIT |
| description | Natural and synthetic biological networks must function reliably in the face of fluctuating stoichiometry of their molecular components. These fluctuations are caused in part by changes in relative expression efficiency and the DNA template amount of the network-coding genes. Gene product levels could potentially be decoupled from these changes via built-in adaptation mechanisms, thereby boosting network reliability. Here, we show that a mechanism based on an incoherent feedforward motif enables adaptive gene expression in mammalian cells. We modeled, synthesized, and tested transcriptional and post-transcriptional incoherent loops and found that in all cases the gene product adapts to changes in DNA template abundance. We also observed that the post-transcriptional form results in superior adaptation behavior, higher absolute expression levels, and lower intrinsic fluctuations. Our results support a previously hypothesized endogenous role in gene dosage compensation for such motifs and suggest that their incorporation in synthetic networks will improve their robustness and reliability. |
| first_indexed | 2024-09-23T13:08:47Z |
| format | Article |
| id | mit-1721.1/77595 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:08:47Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/775952022-09-28T12:11:51Z Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template Bleris, Leonidas Xie, Zhen Glass, David Adadey, Asa Sontag, Eduardo Benenson, Yaakov Massachusetts Institute of Technology. Department of Biological Engineering Xie, Zhen Natural and synthetic biological networks must function reliably in the face of fluctuating stoichiometry of their molecular components. These fluctuations are caused in part by changes in relative expression efficiency and the DNA template amount of the network-coding genes. Gene product levels could potentially be decoupled from these changes via built-in adaptation mechanisms, thereby boosting network reliability. Here, we show that a mechanism based on an incoherent feedforward motif enables adaptive gene expression in mammalian cells. We modeled, synthesized, and tested transcriptional and post-transcriptional incoherent loops and found that in all cases the gene product adapts to changes in DNA template abundance. We also observed that the post-transcriptional form results in superior adaptation behavior, higher absolute expression levels, and lower intrinsic fluctuations. Our results support a previously hypothesized endogenous role in gene dosage compensation for such motifs and suggest that their incorporation in synthetic networks will improve their robustness and reliability. National Institute of General Medical Sciences (U.S.) (Grant GM068763) National Institutes of Health (U.S.) (Grant NIH 1R01GM086881) United States. Air Force Office of Scientific Research (Grant FA9550-08) National Science Foundation (U.S.) (Grant DMS-0614371) 2013-03-07T16:40:54Z 2013-03-07T16:40:54Z 2011-08 2010-12 Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/77595 Bleris, Leonidas et al. “Synthetic Incoherent Feedforward Circuits Show Adaptation to the Amount of Their Genetic Template.” Molecular Systems Biology 7 (2011). en_US http://dx.doi.org/10.1038/msb.2011.49 Molecular Systems Biology Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group Molecular Systems Biology/Nature Publishing Group |
| spellingShingle | Bleris, Leonidas Xie, Zhen Glass, David Adadey, Asa Sontag, Eduardo Benenson, Yaakov Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template |
| title | Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template |
| title_full | Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template |
| title_fullStr | Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template |
| title_full_unstemmed | Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template |
| title_short | Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template |
| title_sort | synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template |
| url | http://hdl.handle.net/1721.1/77595 |
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