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Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression
Figure 6
Dual activation architecture.
(A) Kinetic mechanism of dual activation. The parameters 
and 
are the rates of activator dissociation and association to the operators, and 
is a parameter reflecting the effect of cooperative binding on the dissociation rate. (B) Fano factor as a function of the mean mRNA for independent (
, black), cooperative (
, red), and for simple activation (blue). The parameters are taken from Table 1 and 
, 
, 
, and 
; f is the enhancement factor. (C) A stochastic simulation shows the effect of independent and cooperative binding in creating a sustained state of high promoter activity, resulting in high levels of mRNA in the active state and large cell-to-cell variability. (D) Prediction for the r1-PRM promoter (a PRM promoter variant that does not exhibit OR3 mediated repression [51]). This promoter is activated by cI, which binds cooperatively to OR1 and OR2. The prediction is shown for wild-type cI (
) and for a cooperativity deficient mutant (Y210H, 
). Parameters are taken from [33], [43], [58], [97]. The lifetime of OR1-cI complex is 4 min. Lifetime of OR2-cI complex is 9.5 s.
doi: https://doi.org/10.1371/journal.pcbi.1001100.g006