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Published December 11, 2009 | Accepted Version + Supplemental Material
Journal Article Open

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

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.

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.).

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Accepted Version - nihms160886.pdf

Supplemental Material - mmc1.pdf

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