Abstract
Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.
Highlights
Transcription factors (TFs) are able to locate and bind their target sequence on DNA at surprisingly high rates
While a large majority of subsequent reformulations of this target search problem are based on this facilitated diffusion model [5,6,7,8], there are critical reviews focusing on limitations of the traditional model [9,10]
After finding indirect evidence some years ago, Elf and coworkers recently demonstrated that the lac repressor does display facilitated diffusion in live Escherichia coli (E. coli) cells [19,20]
Summary
Transcription factors (TFs) are able to locate and bind their target sequence on DNA at surprisingly high rates. Afterwards the resulting DNA conformations are centered on a larger lattice representing the full cell volume and remain unchanged during the subsequent simulation of the target search process.
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