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Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression

Figure 2

Simple repression architecture.

(A) Time traces for promoter activity, mRNA and protein copy number are shown for both the weak operator and the strong operator. The mRNA histograms are also shown. The weaker operator with a faster repressor dissociation rate leads to small promoter noise, and an mRNA probability distribution resembling a Poisson distribution (shown by the blue-bar histogram), in which most cells express mRNA near the population average. In contrast, the stronger operator with a slower repressor dissociation rate, leads to larger promoter noise and strongly non-Poissonian mRNA statistics. (B) Kinetic mechanism of repression for an architecture involving a single repressor binding site. The repressor turns off the gene when it binds to the promoter (with rate ), and transcription occurs at a constant rate r when the repressor falls off (with rate ). (C) Normalized variance as a function of the fold-change in mean mRNA copy number. The parameters used are drawn from Table 1. The value of from Table 1 corresponds to the in vitro dissociation constant of the Lac repressor from the Oid operator (black). The results for an off-rate 10-times higher are also plotted (red). As a reference for the size of the fluctuations, we show the normalized variance for a Poisson promoter. (D) Fano factor for two promoters bearing the same off-rates as in (B). Inset. Prediction for the Fano factor for the Δ_O3Δ_O2P_lacUV5 promoter, a variant of the P_lacUV5 promoter for which the two auxiliary operators have been deleted. The fold-change in mRNA noise is plotted as a function of the fold-change in mean mRNA copy number for mutants of the promoter that replace O1 for Oid, O2 or O3. The parameters are taken from Table 1 and [33]. Lifetimes of the operator-repressor complex are 7 min for Oid, 2.4 min for O1, 11s for O2 and 0.47 s for O3. (E) Fold-change in protein noise as a function of the fold-change in mean expression. As expected, the effect of operator strength is the same as observed for mRNA noise.

doi: https://doi.org/10.1371/journal.pcbi.1001100.g002