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

Maximilian Bauer, Emil S. Rasmussen, Michael A. Lomholt, Ralf Metzler
Scientific Reports
5
10072
2015
abstract
Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanismto locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA
and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding
motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a
fast-sliding search state and a recognition state enabling target detection. For the probability to detect the
target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an
auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section.
Importantly, within our model the extent to which the interconversion rates between search and recognition
states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to
distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting
points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several\ørders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs.