Physical constraints determine the logic of bacterial promoter architectures

Abstract

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 organisation 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 organisation we characterise 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.

D.E. and N.R.Z. contributed equally to this work

References in corpus (6)

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• Spatial effects on the speed and reliability of protein-DNA search
• In vivo facilitated diffusion model
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Cited by in corpus (4)

• Transcription factor target site search and gene regulation in a background of unspecific binding sites
• Facilitated diffusion buffers noise in gene expression
• Nonequilibrium model of short-range repression in gene transcription regulation
• Reliable scaling of Position Weight Matrices for binding strength comparisons between transcription factors