Theory on the mechanism of site-specific DNA-protein interactions in the presence of traps

TL;DR

This paper presents a theoretical model explaining how transcription factors efficiently locate their specific DNA binding sites despite the presence of sequence traps, supported by computational analysis of genomic data.

Contribution

The study introduces a simple random walk model predicting trap effects and suggests trap distribution as a metric for identifying TF binding sites.

Findings

Trap arrangement around binding sites minimizes retarding effects.

Condensed DNA conformations reduce trap impact.

Genomic data supports the model's predictions.

Abstract

The speed of site-specific binding of transcription factor (TFs) proteins with genomic DNA seems to be strongly retarded by the randomly occurring sequence traps. Traps are those DNA sequences sharing significant similarity with the original specific binding sites. It is an intriguing question how the naturally occurring TFs and their specific binding sites are designed to manage the retarding effects of such randomly occurring traps. We develop a simple random walk model on the site-specific binding of TFs with genomic DNA in the presence of sequence traps. Our dynamical model predicts that (a) the retarding effects of traps will be minimum when the traps are arranged around the specific binding site such that there is a negative correlation between the binding strength of TFs with traps and the distance of traps from the specific binding site and (b) the retarding effects of sequence traps can be appeased by the condensed conformational state of DNA. Our computational analysis results on the distribution of sequence traps around the putative binding sites of various TFs in mouse and human genome clearly agree well the theoretical predictions. We propose that the distribution of traps can be used as an additional metric to efficiently identify the specific binding sites of TFs on genomic DNA.