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A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator

We develop an exact and flexible mathematical model for Lutz and Bujard’s controllable promoters. It can be used as a building block for modeling genetic systems based on them. Special attention is paid to deduce all the model parameters from reported (in vitro) experimental data. We validate our mo...

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Detalles Bibliográficos
Autores principales: Zamora-Chimal, CG, Zeron, ES
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923745/
https://www.ncbi.nlm.nih.gov/pubmed/25720352
http://dx.doi.org/10.3233/ISB-150465
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author Zamora-Chimal, CG
Zeron, ES
author_facet Zamora-Chimal, CG
Zeron, ES
author_sort Zamora-Chimal, CG
collection PubMed
description We develop an exact and flexible mathematical model for Lutz and Bujard’s controllable promoters. It can be used as a building block for modeling genetic systems based on them. Special attention is paid to deduce all the model parameters from reported (in vitro) experimental data. We validate our model by comparing the regulatory ranges measured in vivo by Lutz and Bujard against the ranges predicted by the model, and which are calculated as the reporter activity obtained under inducing conditions divided by the activity measured under maximal repression. In particular, we verify Bond et al. assertion that the cooperativity between two lac operators can be assumed to be negligible when their central base pairs are separated by 22 or 32 bp [Gene repression by minimal lac loops in vivo, Nucleic Acids Res, 38 (2010) 8072–8082]. Moreover, we also find that the probability that two repressors LacI bind to these operators at the same time can be assumed to be negligible as well. We finally use the model for the promoter P(LlacO-1) to analyze a synthetic genetic oscillator recently build by Stricker et al. [A fast, robust and tunable synthetic gene oscillator, Nature, 456 (2008) 516–519].
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spelling pubmed-49237452016-06-29 A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator Zamora-Chimal, CG Zeron, ES In Silico Biol Research Article We develop an exact and flexible mathematical model for Lutz and Bujard’s controllable promoters. It can be used as a building block for modeling genetic systems based on them. Special attention is paid to deduce all the model parameters from reported (in vitro) experimental data. We validate our model by comparing the regulatory ranges measured in vivo by Lutz and Bujard against the ranges predicted by the model, and which are calculated as the reporter activity obtained under inducing conditions divided by the activity measured under maximal repression. In particular, we verify Bond et al. assertion that the cooperativity between two lac operators can be assumed to be negligible when their central base pairs are separated by 22 or 32 bp [Gene repression by minimal lac loops in vivo, Nucleic Acids Res, 38 (2010) 8072–8082]. Moreover, we also find that the probability that two repressors LacI bind to these operators at the same time can be assumed to be negligible as well. We finally use the model for the promoter P(LlacO-1) to analyze a synthetic genetic oscillator recently build by Stricker et al. [A fast, robust and tunable synthetic gene oscillator, Nature, 456 (2008) 516–519]. IOS Press 2015-07-03 /pmc/articles/PMC4923745/ /pubmed/25720352 http://dx.doi.org/10.3233/ISB-150465 Text en IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zamora-Chimal, CG
Zeron, ES
A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator
title A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator
title_full A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator
title_fullStr A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator
title_full_unstemmed A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator
title_short A simple model for Lutz and Bujard’s controllable promoters and its application for analyzing a simple genetic oscillator
title_sort simple model for lutz and bujard’s controllable promoters and its application for analyzing a simple genetic oscillator
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923745/
https://www.ncbi.nlm.nih.gov/pubmed/25720352
http://dx.doi.org/10.3233/ISB-150465
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