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PMID: 17398098 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Positive-feedback loops as a flexible biological module.

Current biology : CB ·Vol. 17 ·No. 8 ·2007-04-17 ·Pages 668-77

Ingolia NT, Murray AW

Abstract

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. 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. The positive-feedback loop can display several different behaviors, including bistability, and can switch between them as a result of simple mutations.

MeSH Terms
Feedback, Physiological Gene Expression Regulation, Fungal Gene Regulatory Networks MAP Kinase Signaling System Mating Factor Peptides/metabolism Saccharomyces cerevisiae/metabolism
Chemicals
Peptides Mating Factor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ingolia Nicholas T
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Murray Andrew W
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Article Info
Journal
Current biology : CB
Abbr.
Curr Biol
ISSN
0960-9822
DOI
10.1016/j.cub.2007.03.016
Published
2007-04-17
Epub
2007-00-29
Pages
668-77
Language
English
Region
England
NLM ID
9107782
PMCID
PMC1914375
Subset
IM
Grants
NIGMS NIH HHS · P01 GM062566 · United States
NIGMS NIH HHS · P50 GM068763 · United States
NIGMS NIH HHS · GM062566 · United States
NIGMS NIH HHS · GM068763 · United States
Corrections
CommentIn
PMID: 17550765
External Links
PubMed source DOI: 10.1016/j.cub.2007.03.016 PMC Full Text View journal details
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