Sequence-dependent model of genes with dual σ factor preference

Escherichia coli uses s factors to quickly control large gene cohorts during stress conditions. While most of its genes respond to a single s factor, approximately 5% of them have dual s factor preference. The most common are those responsive to both s⁷⁰, which controls housekeeping genes, and s³⁸, which activates genes during stationary growth and stresses. Using RNA-seq and flow-cytometry measurements, we show that 'σ⁷⁰⁺³⁸ genes' are nearly as upregulated in stationary growth as 'σ³⁸ genes'. Moreover, we find a clear quantitative relationship between their promoter sequence and their response strength to changes in σ³⁸ levels. We then propose and validate a sequence dependent model of σ⁷⁰⁺³⁸ genes, with dual sensitivity to s³⁸ and s⁷⁰, that is applicable in the exponential and stationary growth phases, as well in the transient period in between. We further propose a general model, applicable to other stresses and σ factor combinations. Given this, promoters controlling σ⁷⁰⁺³⁸ genes (and variants) could become important building blocks of synthetic circuits with predictable, sequence-dependent sensitivity to transitions between the exponential and stationary growth phases.