| Title: | Positive-feedback loops as a flexible biological module |
| Address: | "Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA" |
| DOI: | 10.1016/j.cub.2007.03.016 |
| ISSN/ISBN: | 0960-9822 (Print) 0960-9822 (Linking) |
| Abstract: | "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" |
| Keywords: | "*Feedback, Physiological *Gene Expression Regulation, Fungal Gene Regulatory Networks *MAP Kinase Signaling System Mating Factor Peptides/*metabolism Saccharomyces cerevisiae/*metabolism;" |
| Notes: | "MedlineIngolia, Nicholas T Murray, Andrew W eng P01 GM062566/GM/NIGMS NIH HHS/ P50 GM068763/GM/NIGMS NIH HHS/ GM062566/GM/NIGMS NIH HHS/ GM068763/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2007/04/03 Curr Biol. 2007 Apr 17; 17(8):668-77. doi: 10.1016/j.cub.2007.03.016. Epub 2007 Mar 29" |
