title: Stochastic pulse regulation in bacterial stress response.
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.
authors: Howard Hughes Medical Institute, Division of Biology and Bioengineering, Broad Center, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors: James C W
authors: JC
authors: Locke
authors: Jonathan W
authors: JW
authors: Young
authors: Michelle
authors: M
authors: Fontes
authors: María Jesús
authors: MJ
authors: Hernández Jiménez
authors: Michael B
authors: MB
authors: Elowitz
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D009173:Mycophenolic Acid / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D013269:Stochastic Processes; D013312:Stress, Physiological; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C086522:RsbV protein, Bacteria; C080358:RsbW protein, bacteria; C079011:SigB protein, Bacteria; D012808:Sigma Factor; C119219:RsbT protein, Bacillus subtilis; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; C091162:RsbU protein, Bacillus subtilis; D009173:Mycophenolic Acid