The incoherent feedforward loop can provide fold-change detection in gene regulation.
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.
Goentoro
Lea
L
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Shoval
Oren
O
Kirschner
Marc W
MW
Alon
Uri
U
D005786:Gene Expression Regulation; D008962:Models, Theoretical; D015398:Signal Transduction