Transcription factor search for a DNA promoter in a three-states model

Abstract

To ensure fast gene activation, Transcription Factors (TF) use a mechanism known as facilitated diffusion to find their DNA promoter site. Here we analyze such a process where a TF alternates between 3D and 1D diffusion. In the latter (TF bound to the DNA), the TF further switches between a fast translocation state dominated by interaction with the DNA backbone, and a slow examination state where interaction with DNA base pairs is predominant. We derive a new formula for the mean search time, and show that it is faster and less sensitive to the binding energy fluctuations compared to the case of a single sliding state. We find that for an optimal search, the time spent bound to the DNA is larger compared to the 3D time in the nucleus, in agreement with recent experimental data. Our results further suggest that modifying switching via phosphorylation or methylation of the TF or the DNA can efficiently regulate transcription.

4 pages, 3 figures

References in corpus (4)

• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• Optimal target search on a fast folding polymer chain with volume exchange
• Searching fast for a target on a DNA without falling to traps
• Thermodynamic restrictions on evolutionary optimization of transcription factor proteins

Cited by in corpus (8)

• Diffusion under time-dependent resetting
• Dynamical transition in the temporal relaxation of stochastic processes under resetting
• Distance matters: the impact of gene proximity in bacterial gene regulation
• Stochastic resetting in underdamped Brownian motion
• Molecular search with conformational change: One-dimensional discrete-state stochastic model
• Facilitated diffusion framework for transcription factor search with conformational changes
• Potential evolutionary advantage of a dissociative search mechanism in DNA mismatch repair
• Arrival time for the fastest among $N$ switching stochastic particles