A general model of the dynamics of genes with dual σ factor preference

Escherichia coli uses the ability of {sigma} factors to recognize specific DNA sequences in order to quickly control large gene cohorts. While most genes respond to only one {sigma} factor, approximately 5% have dual {sigma} factor preference. The ones in significant numbers are {sigma}70+38 genes, responsive to {sigma}70, which controls housekeeping genes, as well as to {sigma}38, which activates genes during stationary growth and stresses. We show that {sigma}70+38 genes are almost as upregulated in stationary growth as genes responsive to {sigma}38 alone. Also, their response strengths to {sigma}38 are predictable from their promoter sequences. Next, we propose a sequence- and {sigma}38 level-dependent, analytical model of {sigma}70+38 genes applicable in the exponential, stationary, and in the transition period between the two growth phases. Finally, we propose a general model, applicable to other {sigma} factors as well. This model can guide the design of synthetic circuits with sequence-dependent sensitivity and plasticity to transitions between the exponential and stationary growth phases. Author SummaryPresent challenges in Synthetic Biology include the design of genetic circuits that are robust to growth phase transitions and whose responsiveness is sequence-dependent, and, thus predictable prior to design. We present and validate an empirical-based, sequence-dependent analytical model of E. coli genes with dual responsiveness to the regulators {sigma}70 and {sigma}38. These genes, supported by our sequence-dependent model, could become building blocks for synthetic genetic circuits functional in both the exponential and the stationary growth phases.