Dissection of the contribution of regulation mode to the properties of feedforward and feedback gene regulatory motifs.

Abstract

We present a framework enabling dissection of the effects of motif structure (feedback or feedforward), nature of the controller (mRNA or protein), and regulation mode (transcriptional, post-transcriptional or translational) on the response to a step change in the input. We have used a common model framework for gene expression where both motif structures have an activating input and repressing regulator, with the same set of parameters to enable comparison of the responses. We studied the global sensitivity of the system properties such as steady-state gain, overshoot, peak time, and peak duration, to parameters. We find that, in all motifs, overshoot correlated negatively whereas peak duration varied concavely, with peak time. Differences in other system properties were found to be mainly dependent on the the nature of the regulator, than the motif structure. Protein mediated motifs showed a higher degree of adaptation; feedforward motifs exhibited perfect adaptation. RNA mediated motifs had a mild regulatory effect; they also exhibited lower peaking tendency and mean overshoot. Protein mediated feedforward motifs showed higher overshoot and lower peak time compared to corresponding feedback motifs.