Laboratory of Biosystem Dynamics, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.
Laboratory of Biosystem Dynamics, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland; Department of Cell and Molecular Biology, Uppsala University, Uppsala 752 37, Sweden.
Biochim Biophys Acta Gene Regul Mech. 2022 Apr;1865(3):194812. doi: 10.1016/j.bbagrm.2022.194812. Epub 2022 Mar 22.
Escherichia coli uses σ factors to quickly control large gene cohorts during stress conditions. While most of its genes respond to a single σ factor, approximately 5% of them have dual σ factor preference. The most common are those responsive to both σ, which controls housekeeping genes, and σ, which activates genes during stationary growth and stresses. Using RNA-seq and flow-cytometry measurements, we show that 'σ genes' are nearly as upregulated in stationary growth as 'σ genes'. Moreover, we find a clear quantitative relationship between their promoter sequence and their response strength to changes in σ levels. We then propose and validate a sequence dependent model of σ genes, with dual sensitivity to σ and σ, 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 σ 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.
大肠杆菌利用σ因子在应激条件下快速控制大量基因簇。虽然其大多数基因对单个σ因子有反应,但大约有 5%的基因具有双σ因子偏好。最常见的是那些对控制管家基因的σ和激活静止生长和应激时基因的σ都有反应的基因。使用 RNA-seq 和流式细胞术测量,我们表明“σ基因”在静止生长时的上调程度几乎与“σ基因”一样。此外,我们发现它们的启动子序列与其对σ水平变化的响应强度之间存在明确的定量关系。然后,我们提出并验证了一个适用于指数和静止生长阶段以及两者之间的瞬态时期的具有对σ和σ双重敏感性的σ基因序列相关模型。我们进一步提出了一个通用模型,适用于其他应激和σ因子组合。有鉴于此,控制σ基因(和变体)的启动子可以成为合成回路的重要构建块,这些回路具有可预测的、序列依赖性的对指数和静止生长阶段之间转换的敏感性。