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<datestamp>2017-12-21</datestamp>
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<publisher>HAL CCSD</publisher>
<title lang=en>Kinetic approaches to lactose operon induction and bimodality.</title>
<creator>Michel, Denis</creator>
<contributor>TREC : Transcription, Environment and Cancer ; Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) - Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<description>International audience</description>
<source>ISSN: 0022-5193</source>
<source>EISSN: 1095-8541</source>
<source>Journal of Theoretical Biology</source>
<publisher>Elsevier</publisher>
<identifier>inserm-00818506</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00818506</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00818506/document</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00818506/file/LacI-TeX.pdf</identifier>
<source>http://www.hal.inserm.fr/inserm-00818506</source>
<source>Journal of Theoretical Biology, Elsevier, 2013, 325, pp.62-75. 〈10.1016/j.jtbi.2013.02.005〉</source>
<identifier>ARXIV : 1312.5566</identifier>
<relation>info:eu-repo/semantics/altIdentifier/arxiv/1312.5566</relation>
<identifier>DOI : 10.1016/j.jtbi.2013.02.005</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jtbi.2013.02.005</relation>
<identifier>PUBMED : 23454080</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/23454080</relation>
<language>en</language>
<subject lang=en>Lactose operon</subject>
<subject lang=en>Induction threshold</subject>
<subject lang=en>Single rebinding interval</subject>
<subject>[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology</subject>
<subject>[PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]</subject>
<subject>[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]</subject>
<subject>[INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>The quasi-equilibrium approximation is acceptable when molecular interactions are fast enough compared to circuit dynamics, but is no longer allowed when cellular activities are governed by rare events. A typical example is the lactose operon (lac), one of the most famous paradigms of transcription regulation, for which several theories still coexist to describe its behaviors. The lac system is generally analyzed by using equilibrium constants, contradicting single-event hypotheses long suggested by Novick and Weiner (1957). Enzyme induction as an all-or-none phenomenon. Proc. Natl. Acad. Sci. USA 43, 553-566) and recently refined in the study of (Choi et al., 2008. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science 322, 442-446). In the present report, a lac repressor (LacI)-mediated DNA immunoprecipitation experiment reveals that the natural LacI-lac DNA complex built in vivo is extremely tight and long-lived compared to the time scale of lac expression dynamics, which could functionally disconnect the abortive expression bursts and forbid using the standard modes of lac bistability. As alternatives, purely kinetic mechanisms are examined for their capacity to restrict induction through: (i) widely scattered derepression related to the arrival time variance of a predominantly backward asymmetric random walk and (ii) an induction threshold arising in a single window of derepression without recourse to nonlinear multimeric binding and Hill functions. Considering the complete disengagement of the lac repressor from the lac promoter as the probabilistic consequence of a transient stepwise mechanism, is sufficient to explain the sigmoidal lac responses as functions of time and of inducer concentration. This sigmoidal shape can be misleadingly interpreted as a phenomenon of equilibrium cooperativity classically used to explain bistability, but which has been reported to be weak in this system.</description>
<date>2013-05-21</date>
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