In vivo facilitated diffusion model

Abstract

Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.

19 pages, 9 figures, Supplementary Information directly included

References in corpus (6)

• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• Subdiffusion and weak ergodicity breaking in the presence of a reactive boundary
• Spatial effects on the speed and reliability of protein-DNA search
• Spatial and topological organization of DNA chains induced by gene co-localization
• Effects of intersegmental transfers on target location by proteins
• Facilitated diffusion on confined DNA

Cited by in corpus (27)

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• First passage time statistics for two-channel diffusion
• The effects of transcription factor competition on gene regulation
• Search reliability and search efficiency of combined Lévy-Brownian motion: long relocations mingled with thorough local exploration
• Optimization and universality of Brownian search in quenched heterogeneous media
• Energetic funnel facilitates facilitated diffusion
• Sequence Heterogeneity Accelerates Protein Search for Targets on DNA
• Physical constraints determine the logic of bacterial promoter architectures
• Optimization of random search processes in the presence of an external bias
• Comparison of pure and combined search strategies for single and multiple targets
• Protein search for multiple targets on DNA
• Search efficiency in the Adam-Delbrück reduction-of-dimensionality scenario versus direct diffusive search
• Molecular search with conformational change: One-dimensional discrete-state stochastic model
• Target search on DNA by interacting molecules: First-passage approach
• A mini-review of the diffusion dynamics of DNA-binding proteins: Experiments and models
• Active transport improves the precision of linear long distance molecular signalling
• Controlling Uncertainty of Empirical First-Passage Times in the Small-Sample Regime
• Theory on the mechanism of site-specific DNA-protein interactions in the presence of traps
• Modelling Protein Target-Search in Human Chromosomes
• Transition from distributional to ergodic behavior in an inhomogeneous diffusion process: Method revealing an unknown surface diffusivity
• First-passage dynamics of obstructed tracer particle diffusion in one-dimensional systems
• Concentration of Empirical First-Passage Times
• Surface-Facilitated Trapping by Active Sites: From Catalysts to Viruses
• Variance-corrected Michaelis-Menten equation predicts transient rates of single-enzyme reactions and response times in bacterial gene-regulation