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Physical constraints determine the logic of bacterial promoter architectures

Published version
Peer-reviewed

Type

Article

Change log

Authors

Ezer, D 
Zabet, NR 
Adryan, B 

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.

Description

Keywords

Binding Sites, Escherichia coli, Promoter Regions, Genetic, Transcription Factors

Journal Title

Nucleic Acids Research

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

42

Publisher

Oxford University Press
Sponsorship
Medical Research Council (G1002110)