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Recent experiments show that transcription factors (TFs) indeed use thefacilitated diffusion mechanism to locate their target sequences on DNA inliving bacteria cells: TFs alternate between sliding motion along DNA andrelocation events through the cytoplasm. From simulations and theoreticalanalysis we study the TF-sliding motion for a large section of the DNA-sequenceof a common E. coli strain, based on the two-state TF-model with a fast-slidingsearch state and a recognition state enabling target detection. For theprobability to detect the target before dissociating from DNA the TF-searchtimes self-consistently depend heavily on whether or not an auxiliary operator(an accessible sequence similar to the main operator) is present in the genomesection. Importantly, within our model the extent to which the interconversionrates between search and recognition states depend on the underlying nucleotidesequence is varied. A moderate dependence maximises the capability todistinguish between the main operator and similar sequences. Moreover, theseauxiliary operators serve as starting points for DNA looping with the mainoperator, yielding a spectrum of target detection times spanning several ordersof magnitude. Auxiliary operators are shown to act as funnels facilitatingtarget detection by TFs.

Real sequence effects on the search dynamics of transcription factors on DNA