Stochastic Pulse Regulation in Bacterial Stress Response
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.
Additional Information© 2011 American Association for the Advancement of Science. Received for publication 10 May 2011. Accepted for publication 1 September 2011. We thank C. Price and D. Rudner for providing strains. We thank A. Eldar, R. Kishony, C. Price, N. Wingreen, J. Levine, and other members of M.B.E's laboratory for helpful discussions. Work in M.B.E's laboratory was supported by NIH grants R01GM079771 and P50 GM068763, U.S. National Science Foundation CAREER Award 0644463, and the Packard Foundation. J.C.W.L was supported by the International Human Frontier Science Program Organization and the European Molecular Biology Organization.
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