Dose Response Relationship in Anti-Stress Gene Regulatory Networks
Figure 9
Variations in the Pre-Transcriptional Local Gain (r1), Level of Constitutive Activation, Earliness of Saturation of Gene Activation, and Degree of Feedforward Activation Can Qualitatively Alter the Curvature of the Y versus Se (External Stress) Dose Response Curve in the Low-Dose Region
(A) Relatively small r1, high constitutive activation, and large Kd tend to retain the superlinear appearance in the low-dose region.
(B) Intermediate conditions lead to minimal curvature change.
(C) Relatively large r1, small constitutive activation, and small Kd render a sublinear appearance in the low-dose region.
(D) Introduction of feedforward activation can depress Y initially, giving rise to a J-shaped dose response.
Note: solid lines are simulation results, dashed straight lines were drawn to show how linear extrapolation from the high-dose region to the basal level can mis-estimate the response at low doses. Saturation of gene activation was modeled by changing Kd for transcription factor T binding to the gene promoter.