Positive-feedback loops as a flexible biological module.
BACKGROUND
Bistability in genetic networks allows cells to remember past events and to make discrete decisions in response to graded signals. Bistable behavior can result from positive feedback, but feedback loops can have other roles in signal transduction as well.


RESULTS
We introduced positive feedback into the budding-yeast pheromone response to convert it into a bistable system. In the presence of feedback, transient induction with high pheromone levels caused persistent pathway activation, whereas at lower levels a fraction of cells became persistently active but the rest inactivated completely. We also generated mutations that quantitatively tuned the basal and induced expression levels of the feedback promoter and showed that they qualitatively changed the behavior of the system. Finally, we developed a simple stochastic model of our positive-feedback system and showed the agreement between our simulations and experimental results.


CONCLUSIONS
The positive-feedback loop can display several different behaviors, including bistability, and can switch between them as a result of simple mutations.
Ingolia
Nicholas T
NT
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Murray
Andrew W
AW
D025461:Feedback, Physiological; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D020935:MAP Kinase Signaling System; D000072235:Mating Factor; D010455:Peptides / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D010455:Peptides; D000072235:Mating Factor