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Stochastic Stabilization of Phenotypic States: The Genetic Bistable Switch as a Case Study

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  • Marc Weber
  • Javier Buceta

Abstract

We study by means of analytical calculation and stochastic simulations how intrinsic noise modifies the bifurcation diagram of gene regulatory processes that can be effectively described by the Langevin formalism. In a general context, our study raises the intriguing question of how biochemical fluctuations redesign the epigenetic landscape in differentiation processes. We have applied our findings to a general class of regulatory processes that includes the simplest case that displays a bistable behavior and hence phenotypic variability: the genetic auto-activating switch. Thus, we explain why and how the noise promotes the stability of the low-state phenotype of the switch and show that the bistable region is extended when increasing the intensity of the fluctuations. This phenomenology is found in a simple one-dimensional model of the genetic switch as well as in a more detailed model that takes into account the binding of the protein to the promoter region. Altogether, we prescribe the analytical means to understand and quantify the noise-induced modifications of the bifurcation points for a general class of regulatory processes where the genetic bistable switch is included.

Suggested Citation

  • Marc Weber & Javier Buceta, 2013. "Stochastic Stabilization of Phenotypic States: The Genetic Bistable Switch as a Case Study," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-8, September.
    • Handle: RePEc:plo:pone00:0073487
    DOI: 10.1371/journal.pone.0073487
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    References listed on IDEAS

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    2. Long Cai & Chiraj K. Dalal & Michael B. Elowitz, 2008. "Frequency-modulated nuclear localization bursts coordinate gene regulation," Nature, Nature, vol. 455(7212), pages 485-490, September.
    3. Ertugrul M. Ozbudak & Mukund Thattai & Han N. Lim & Boris I. Shraiman & Alexander van Oudenaarden, 2004. "Multistability in the lactose utilization network of Escherichia coli," Nature, Nature, vol. 427(6976), pages 737-740, February.
    4. Timothy S. Gardner & Charles R. Cantor & James J. Collins, 2000. "Construction of a genetic toggle switch in Escherichia coli," Nature, Nature, vol. 403(6767), pages 339-342, January.
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