title: Transcription factor search for a DNA promoter in a three-state model.
abstract: To ensure fast gene activation, transcription factors (TFs) use a mechanism known as facilitated diffusion to find their DNA promoter site. Here we analyze such a process where a TF alternates between three- and one-dimensional 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 (bp) is predominant. We derive a formula for the mean search time, and show that it is faster and less sensitive to the binding-energy fluctuations as compared to the case with a single sliding state. We find that for an optimal search, the time spent bound to the DNA is larger compared to the three-dimensional time, in agreement with recent experimental data.
authors.affiliation: Department of Computational Biology, (IBENS) Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Reingruber
authors.forename: David
authors.initials: D
authors.lastname: Holcman
mesh_terms: D004247:DNA / Q000235:genetics* / Q000378:metabolism*; D004058:Diffusion; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D004247:DNA