title: 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.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lea
authors.initials: L
authors.lastname: Goentoro
authors.forename: Oren
authors.initials: O
authors.lastname: Shoval
authors.forename: Marc W
authors.initials: MW
authors.lastname: Kirschner
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D005786:Gene Expression Regulation; D008962:Models, Theoretical; D015398:Signal Transduction