Ab initio thermodynamic modeling of distal multisite transcription regulation Journal Article
| Authors: | Saiz, L.; Vilar, J. M. G. |
| Article Title: | Ab initio thermodynamic modeling of distal multisite transcription regulation |
| Abstract: | Transcription regulation typically involves the binding of proteins over long distances on multiple DNA sites that are brought close to each other by the formation of DNA loops. The inherent complexity of assembling regulatory complexes on looped DNA challenges the understanding of even the simplest genetic systems, including the prototypical lac operon. Here we implement a scalable approach based on thermodynamic molecular properties to model ab initio systems regulated through multiple DNA sites with looping. We show that this approach applied to the lac operon accurately predicts the system behavior for a wide range of cellular conditions, which include the transcription rate over five orders of magnitude as a function of the repressor concentration for wild type and all seven combinations of deletions of three operators, as well as the observed induction curves for cells with and without active catabolite activator protein. Our results provide new insights into the detailed functioning of the lac operon and reveal an efficient avenue to incorporate the required underlying molecular complexity into fully predictive models of gene regulation. © 2007 The Author(s). |
| Keywords: | gene deletion; nonhuman; computational biology; protein dna binding; transcription, genetic; wild type; dna; transcription regulation; escherichia coli; gene control; models, genetic; thermodynamics; repressor proteins; dna, bacterial; gene expression regulation, bacterial; lactose operon; lac operon; repressor gene; cyclic amp binding protein; cyclic amp receptor protein; ab initio calculation; operator gene; isopropyl thiogalactoside; operator regions (genetics) |
| Journal Title: | Nucleic Acids Research |
| Volume: | 36 |
| Issue: | 3 |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Date Published: | 2008-02-01 |
| Start Page: | 726 |
| End Page: | 731 |
| Language: | English |
| DOI: | 10.1093/nar/gkm1034 |
| PUBMED: | 18056082 |
| PROVIDER: | scopus |
| PMCID: | PMC2241893 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: NARHA" - "Source: Scopus" |
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Gomez Vilar
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