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The incoherent feedforward loop can provide fold-change detection in gene regulation

Goentoro, Lea and Shoval, Oren and Kirschner, Marc W. and Alon, Uri (2009) The incoherent feedforward loop can provide fold-change detection in gene regulation. Molecular Cell, 36 (5). pp. 894-9. ISSN 1097-2765. PMCID PMC2896310. https://resolver.caltech.edu/CaltechAUTHORS:20150616-090522646

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Abstract

Many sensory systems (e.g., vision and hearing) show a response that is proportional to the fold-change in the stimulus relative to the background, a feature related to Weber's Law. Recent experiments suggest such a fold-change detection feature in signaling systems in cells: a response that depends on the fold-change in the input signal, and not on its absolute level. It is therefore of interest to find molecular mechanisms of gene regulation that can provide such fold-change detection. Here, we demonstrate theoretically that fold-change detection can be generated by one of the most common network motifs in transcription networks, the incoherent feedforward loop (I1-FFL), in which an activator regulates both a gene and a repressor of the gene. The fold-change detection feature of the I1-FFL applies to the entire shape of the response, including its amplitude and duration, and is valid for a wide range of biochemical parameters.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.molcel.2009.11.018DOIArticle
http://www.sciencedirect.com/science/article/pii/S1097276509008594PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896310/PubMed CentralArticle
ORCID:
AuthorORCID
Goentoro, Lea0000-0002-3904-0195
Additional Information:© 2009 Elsevier. Received 20 August 2009, Revised 13 November 2009, Accepted 18 November 2009, Available online 10 December 2009. Published: December 10, 2009. For suggestions and critical reading of the manuscript, the authors thank Cellina Cohen-Saidon, Michael Springer, Eduardo Sontag, Jessica Gray, and Adam Palmer. O.S. is grateful to the Azrieli Foundation for the award of an Azrieli Fellowship. L.G. is a Robert Black Fellow of the Damon Runyon Foundation (DRG-1958-07). This work was supported by the Kahn Family Foundation (U.A.), R01 HD037277 (M.W.K.), the Novartis-Harvard-Hebrew University program (M.W.K.), and the Israel Science Foundation (U.A.).
Funders:
Funding AgencyGrant Number
Azrieli FoundationUNSPECIFIED
Damon Runyon Cancer Research FoundationDRG-1958-07
Kahn Family Foundation UNSPECIFIED
NIHR01 HD037277
Novartis-Harvard-Hebrew University programUNSPECIFIED
Israel Science FoundationUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC2896310
Record Number:CaltechAUTHORS:20150616-090522646
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150616-090522646
Official Citation:Lea Goentoro, Oren Shoval, Marc W. Kirschner, Uri Alon, The Incoherent Feedforward Loop Can Provide Fold-Change Detection in Gene Regulation, Molecular Cell, Volume 36, Issue 5, 11 December 2009, Pages 894-899, ISSN 1097-2765, http://dx.doi.org/10.1016/j.molcel.2009.11.018. (http://www.sciencedirect.com/science/article/pii/S1097276509008594)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58275
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:16 Jun 2015 17:32
Last Modified:03 Oct 2019 08:34

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