Energetic funnel facilitates facilitated diffusion

Abstract

Transcription factors are able to associate to their binding sites on DNA faster than the physical limit posed by diffusion. Such high association rates can be achieved by alternating between three-dimensional diffusion and one-dimensional sliding along the DNA chain, a mechanism dubbed Facilitated Diffusion. By studying a collection of transcription factor binding sites of Escherichia coli from the RegulonDB database and of Bacillus subtilis from DBTBS, we reveal a funnel in the binding energy landscape around the target sequences. We show that such a funnel is linked to the presence of gradients of AT in the base composition in the DNA region around the binding sites. An extensive computational study of the stochastic sliding process along the energetic landscapes obtained from the database shows that the funnel can significantly enhance the probability of transcription factors to find their target sequences when sliding in their proximity. We demonstrate that this enhancement leads to a speed-up of the association process.

10 pages, Nucleic Acids Research in press. Supplementary information available from the Journal (at https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkx1220/4690584)

References in corpus (6)

• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• Facilitated diffusion on mobile DNA: configurational traps and sequence heterogeneity
• Effects of intersegmental transfers on target location by proteins
• Comparison of kinetic and dynamical models of DNA-protein interaction and facilitated diffusion
• Genome-wide organization of eukaryotic pre-initiation complex is influenced by nonconsensus protein-DNA binding
• Real sequence effects on the search dynamics of transcription factors on DNA