PT - JOURNAL ARTICLE AU - Bharat Ravi Iyengar AU - Beena Pillai AU - K.V. Venkatesh AU - Chetan J. Gadgil TI - Dissection of the contribution of regulation mode to the properties of feedforward and feedback gene regulatory motifs AID - 10.1101/065698 DP - 2016 Jan 01 TA - bioRxiv PG - 065698 4099 - http://biorxiv.org/content/early/2016/11/22/065698.short 4100 - http://biorxiv.org/content/early/2016/11/22/065698.full AB - 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 simple model of gene expression where both motif structures have an activating input and repressing regulator. We generated 10000 parameter sets centered around a default set, by random multivariate sampling. Analysis of the different motifs was done with each of these parameter sets (common for all motifs) to assess global sensitivity of system properties, studied using metrics like steady-state gain, overshoot, peak time, and peak duration, to parameters. Protein mediated motifs showed higher degree of adaptation; feedforward motifs especially, 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 feedforward motifs. However, in all motifs, overshoot correlated negatively whereas peak duration varied concavely, with peak time.