Dissecting specific and global transcriptional regulation of bacterial gene expression
Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional—but often neglected—layer of complexity in gene expression. Here, we develop an experiment...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2013-01-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2013.14 |
| _version_ | 1797280276867448832 |
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| author | Luca Gerosa Karl Kochanowski Matthias Heinemann Uwe Sauer |
| author_facet | Luca Gerosa Karl Kochanowski Matthias Heinemann Uwe Sauer |
| author_sort | Luca Gerosa |
| collection | DOAJ |
| description | Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional—but often neglected—layer of complexity in gene expression. Here, we develop an experimental‐computational approach to dissect specific and global regulation in the bacterium Escherichia coli. By using fluorescent promoter reporters, we show that global regulation is growth rate dependent not only during steady state but also during dynamic changes in growth rate and can be quantified through two promoter‐specific parameters. By applying our approach to arginine biosynthesis, we obtain a quantitative understanding of both specific and global regulation that allows accurate prediction of the temporal response to simultaneous perturbations in arginine availability and growth rate. We thereby uncover two principles of joint regulation: (i) specific regulation by repression dominates the transcriptional response during metabolic steady states, largely repressing the biosynthesis genes even when biosynthesis is required and (ii) global regulation sets the maximum promoter activity that is exploited during the transition between steady states. |
| first_indexed | 2024-03-07T16:37:49Z |
| format | Article |
| id | doaj.art-d2e05f538e2f43a8ba409bbf5e49a2d2 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:37:49Z |
| publishDate | 2013-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-d2e05f538e2f43a8ba409bbf5e49a2d22024-03-03T09:32:04ZengSpringer NatureMolecular Systems Biology1744-42922013-01-0191n/an/a10.1038/msb.2013.14Dissecting specific and global transcriptional regulation of bacterial gene expressionLuca Gerosa0Karl Kochanowski1Matthias Heinemann2Uwe Sauer3Institute of Molecular Systems Biology, ETH Zurich Zurich SwitzerlandInstitute of Molecular Systems Biology, ETH Zurich Zurich SwitzerlandInstitute of Molecular Systems Biology, ETH Zurich Zurich SwitzerlandInstitute of Molecular Systems Biology, ETH Zurich Zurich SwitzerlandGene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional—but often neglected—layer of complexity in gene expression. Here, we develop an experimental‐computational approach to dissect specific and global regulation in the bacterium Escherichia coli. By using fluorescent promoter reporters, we show that global regulation is growth rate dependent not only during steady state but also during dynamic changes in growth rate and can be quantified through two promoter‐specific parameters. By applying our approach to arginine biosynthesis, we obtain a quantitative understanding of both specific and global regulation that allows accurate prediction of the temporal response to simultaneous perturbations in arginine availability and growth rate. We thereby uncover two principles of joint regulation: (i) specific regulation by repression dominates the transcriptional response during metabolic steady states, largely repressing the biosynthesis genes even when biosynthesis is required and (ii) global regulation sets the maximum promoter activity that is exploited during the transition between steady states.https://doi.org/10.1038/msb.2013.14expression machinerymodellingsynthetic biologytranscriptional circuittranscriptional regulation |
| spellingShingle | Luca Gerosa Karl Kochanowski Matthias Heinemann Uwe Sauer Dissecting specific and global transcriptional regulation of bacterial gene expression Molecular Systems Biology expression machinery modelling synthetic biology transcriptional circuit transcriptional regulation |
| title | Dissecting specific and global transcriptional regulation of bacterial gene expression |
| title_full | Dissecting specific and global transcriptional regulation of bacterial gene expression |
| title_fullStr | Dissecting specific and global transcriptional regulation of bacterial gene expression |
| title_full_unstemmed | Dissecting specific and global transcriptional regulation of bacterial gene expression |
| title_short | Dissecting specific and global transcriptional regulation of bacterial gene expression |
| title_sort | dissecting specific and global transcriptional regulation of bacterial gene expression |
| topic | expression machinery modelling synthetic biology transcriptional circuit transcriptional regulation |
| url | https://doi.org/10.1038/msb.2013.14 |
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