Controlling gene expression timing through gene regulatory architecture
Fig 6
Expression timing of target gene is dictated by the nature of TF regulation.
(A, B) MFPT of a target gene as a function of binding affinity of TF to the target gene (koff,t). Filled symbols represent the TF being auto-activated (α > 1), open symbols represent when the TF gene is auto-repressed (α < 1), and black filled circles are when the TF gene is constitutive (α = 1). Circles represent target gene activation whereas squares represent target gene being repressed by the TF gene. (C) MFPT of target gene as a function of MFPT of TF gene. α is varied from from 0 to 50 while keeping koff = 0.002 s−1 and koff,t = 0.2 s−1 constant. The MFPTs of TF and target genes are normalized by their respective MFPTs when α is one or equivalently when TF gene is constitutive. Translation rate of the TF gene is adjusted to achieve constant level of TF number (∼50) for varying binding affinities and α in (A-C). The target gene is purely activated or repressed, i.e., when a TF is bound to target gene it is expressed in the case of activation and is completely repressed in the case of repression. Parameter used for target gene: r0,t = 0, rt = 0.05 s−1, b = 0.1 s−1mRNA−1 (target activation), r0,t = 0.05 s−1, rt = 0, b = 0.1 s−1mRNA−1 (target repression). (D) Plot showing asymmetry in the expression timing of TF and target gene when they have identical binding affinity, transcription and translation rates. Target gene repressed by an auto-repressed TF gene always has higher MFPT compared to the TF gene. TF binding affinity is tuned to generate the curves. Target gene activated by an auto-activated TF gene, on contrary, do not show any significant differences (target gene being moderately faster than the TF gene). Parameters: r0 = r0,t = 0.025 s−1, b = 0.1 s−1mRNA−1. Binding affinity is varied to generate the curve.