Steady-state expression of self-regulated genes

Fournier, Thomas; Gabriel, Jean-Pierre; Mazza, Christian; Pasquier, Jérôme; Galbete, J.L.; Mermod, Nicolas

doi:10.1093/bioinformatics/btm490

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Journal article

Steady-state expression of self-regulated genes

Fournier, Thomas Department of Mathematics, University of Fribourg, Switzerland
Gabriel, Jean-Pierre Department of Mathematics, University of Fribourg, Switzerland
Mazza, Christian Department of Mathematics, University of Fribourg, Switzerland
Pasquier, Jérôme Department of Mathematics, University of Fribourg, Switzerland
Galbete, J.L. Institute of Biotechnology, University of Lausanne, Switzerland
Mermod, Nicolas Institute of Biotechnology, University of Lausanne, Switzerland

12.10.2007

Published in:

Bioinformatics. - 2007, vol. 23, no. 23, p. 3185-3192

English Motivation: Regulatory gene networks contain generic modules such as feedback loops that are essential for the regulation of many biological functions. The study of the stochastic mechanisms of gene regulation is instrumental for the understanding of how cells maintain their expression at levels commensurate with their biological role, as well as to engineer gene expression switches of appropriate behavior. The lack of precise knowledge on the steady-state distribution of gene expression requires the use of Gillespie algorithms and Monte-Carlo approximations. Methodology: In this study, we provide new exact formulas and efficient numerical algorithms for computing/modeling the steady-state of a class of self-regulated genes, and we use it to model/compute the stochastic expression of a gene of interest in an engineered network introduced in mammalian cells. The behavior of the genetic network is then analyzed experimentally in living cells. Results: Stochastic models often reveal counter-intuitive experimental behaviors, and we find that this genetic architecture displays a unimodal behavior in mammalian cells, which was unexpected given its known bimodal response in unicellular organisms. We provide a molecular rationale for this behavior, and we implement it in the mathematical picture to explain the experimental results obtained from this network.

Faculty

Faculté des sciences et de médecine

Department

Département de Mathématiques

Language