Stochastic Pulse Regulation in Bacterial Stress Response

Howard Hughes Medical Institute, Division of Biology and Bioengineering, Broad Center, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Science (Impact Factor: 31.48). 10/2011; 334(6054):366-9. DOI: 10.1126/science.1208144
Source: PubMed

ABSTRACT Gene regulatory circuits can use dynamic, and even stochastic, strategies to respond to environmental conditions. We examined activation of the general stress response mediated by the alternative sigma factor, σ(B), in individual Bacillus subtilis cells. We observed that energy stress activates σ(B) in discrete stochastic pulses, with increasing levels of stress leading to higher pulse frequencies. By perturbing and rewiring the endogenous system, we found that this behavior results from three key features of the σ(B) circuit: an ultrasensitive phosphorylation switch; stochasticity ("noise"), which activates that switch; and a mixed (positive and negative) transcriptional feedback, which can both amplify a pulse and switch it off. Together, these results show how prokaryotes encode signals using stochastic pulse frequency modulation through a compact regulatory architecture.

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    • "The combination of positive and negative feedback regulation provides a mechanism to regulate the strength and duration of a response [10] (Fig. 1E). For instance, the Bacillus subtilis energy stress response involving the alternative sigma factor B is temporally modulated by stochastic pulses of gene activation with the strength of the response controlled by the frequency, not the magnitude of the pulses [15]. Stochastic fluctuations in the concentration of a phosphatase serve as the pulse trigger. "
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