Physical constraints determine the logic of bacterial promoter architectures.
Site-specific transcription factors (TFs) bind to their target sites on the DNA, where they regulate the rate at which genes are transcribed. Bacterial TFs undergo facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA) when searching for their target sites. Using computer simulations of this search process, we show that the organization of the binding sites, in conjunction with TF copy number and binding site affinity, plays an important role in determining not only the steady state of promoter occupancy, but also the order at which TFs bind. These effects can be captured by facilitated diffusion-based models, but not by standard thermodynamics. We show that the spacing of binding sites encodes complex logic, which can be derived from combinations of three basic building blocks: switches, barriers and clusters, whose response alone and in higher orders of organization we characterize in detail. Effective promoter organizations are commonly found in the E. coli genome and are highly conserved between strains. This will allow studies of gene regulation at a previously unprecedented level of detail, where our framework can create testable hypothesis of promoter logic.
Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK and Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Daphne
D
Ezer
Nicolae Radu
NR
Zabet
Boris
B
Adryan
D001665:Binding Sites; D004926:Escherichia coli / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors