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      Stochasticity in Transcriptional Regulation: Origins, Consequences, and Mathematical Representations

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      Biophysical Journal

      Elsevier BV

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          Abstract

          Transcriptional regulation is an inherently noisy process. The origins of this stochastic behavior can be traced to the random transitions among the discrete chemical states of operators that control the transcription rate and to finite number fluctuations in the biochemical reactions for the synthesis and degradation of transcripts. We develop stochastic models to which these random reactions are intrinsic and a series of simpler models derived explicitly from the first as approximations in different parameter regimes. This innate stochasticity can have both a quantitative and qualitative impact on the behavior of gene-regulatory networks. We introduce a natural generalization of deterministic bifurcations for classification of stochastic systems and show that simple noisy genetic switches have rich bifurcation structures; among them, bifurcations driven solely by changing the rate of operator fluctuations even as the underlying deterministic system remains unchanged. We find stochastic bistability where the deterministic equations predict monostability and vice-versa. We derive and solve equations for the mean waiting times for spontaneous transitions between quasistable states in these switches.

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          Author and article information

          Journal
          Biophysical Journal
          Biophysical Journal
          Elsevier BV
          00063495
          December 2001
          December 2001
          : 81
          : 6
          : 3116-3136
          Article
          10.1016/S0006-3495(01)75949-8
          1301773
          11720979
          © 2001

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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