| Method |
"A key question is whether such facilitated diffusion occurs in living
cells. Recent single-molecule experiments suggest that it does. During
the search process, a transcription factor spends 90% of its time on
nonspecific DNA, and the residence time of nonspecific binding is less
than 5 ms (ref. 35). Given the 1D diffusion constant in vitro, the protein
inspects ~100 base pairs (bp), which implies a 100-fold acceleration of target search compared with the case with no 1D diffusion (ref 52). This observation is consistent with mounting evidence that the length of the DNA segment that a transcription factor inspects is shorter than 1,000 bp (refs 53–57), the value estimated from early in vitro experiments (ref 43). This 100-bp range indicates that for a 5×10^6 bp genome, a transcription factor must inspect 5×10^6/100=5×10^4 segments before reaching the target site. Therefore, the total search time for one transcription factor in a cell is ~5×10^4×5 ms = 250 s, in close agreement with the measured search time (ref 35)." |