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Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression
Figure 5
Simple activation architecture.
(A) The Fano factor is plotted as a function of the fold-change gene expression (blue line). In red, we show the effect of reducing operator strength (i.e., reducing the lifetime of the operator-activator complex) by a factor of 10. Just as we observed with single repression, weak activator binding operators generate less promoter noise than strong activating operators. The parameters used are shown in Table 1 with the exception of 
, where f is the enhancement factor. Inset: Prediction for the activation of the Plac promoter. The fold-change in noise is plotted as a function of the fold-change in mean mRNA expression for both the wild-type Plac (CRP dissociation time = 8 min), represented by a blue line, and a Plac promoter variant where the lac CRP binding site has been replaced by the weaker gal CRP binding site (dissociation time = 1 min). The enhancement factor was set to 
[33]. These parameters are taken from [67] and [33]. The remaining parameters are taken from Table 1. (B) Fano factor as a function of 
for a repressor (black) and an activator (red) with the same transcription factor affinity. The transcription rate in the absence of activator is assumed to be zero. The transcription rate in the fully activated case is equal to the transcription rate of the repression construct in the absence of repressor and is 
as specified by Table 1. For low expression levels 
simple activation is considerably noisier than simple repression. (C) The results of a stochastic simulation for the simple activation and simple repression architectures. We assume identical dissociation rates for the activator and repressor, and identical rates of transcription in their respective active states. As shown in (B), low concentrations of an activator result in few, but very productive transcription events, whereas high concentrations of a repressor lead to the frequent but short lived excursions into the active state.
doi: https://doi.org/10.1371/journal.pcbi.1001100.g005