Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations.

Published

Journal Article

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.

Full Text

Cited Authors

  • Kepler, TB; Elston, TC

Published Date

  • December 2001

Published In

Volume / Issue

  • 81 / 6

Start / End Page

  • 3116 - 3136

PubMed ID

  • 11720979

Pubmed Central ID

  • 11720979

International Standard Serial Number (ISSN)

  • 0006-3495

Digital Object Identifier (DOI)

  • 10.1016/S0006-3495(01)75949-8

Language

  • eng

Conference Location

  • United States