A feedforward loop motif in transcriptional regulation: induction and repression

We study the dynamical behavior of a unit of three positive transcriptional regulators which occurs frequently in biological networks of yeast and bacteria as a feedforward loop. We investigate numerically a set of reactions incorporating the basic features of transcription and translation. We determine (i) how the feedforward loop motif functions as a computational element such as an AT D gate in the presence of stochastic fluctuations, and (ii) the robustness of the motif when transcription at the primary level is suddenly repressed. We highlight the effective time-scales which underlie both of these aspects of the feedforward loop motif. We show how threshold behavior of the motif output arises as a function of the number of external inducers as well as the time over which the inducer acts. We discuss how individual cell behavior can deviate significantly from average behavior, due to intrinsic fluctuations in the small number of molecules present in a cell. (C) 2004 Elsevier Ltd. All rights reserved.