  The model of facilitated diffusion describes how DNA-binding proteins, such
as transcription factors (TFs), find their chromosomal targets by combining 3D
diffusion through the cytoplasm and 1D sliding along nonspecific DNA sequences.
The redundant 1D diffusion near the specific binding site extends the target
size and facilitates target location. While this model successfully predicts
the kinetics measured in test tubes, it has not been extended to account for
the highly crowded environment in living cells. Here, we investigate the effect
of other DNA-binding proteins that partially occupy the bacterial chromosome.
We show how they would slow down the search process, mainly through restricted
sliding near the target. This implies that increasing the overall DNA-binding
protein concentration would have a marginal effect in reducing the search time,
because any additional proteins would restrict the search process for each
other. While the presence of other proteins prevents sliding from the flanking
DNA, DNA looping provides an alternative path to transfer from neighboring
sites to the target efficiently. We propose that, when looping is faster than
the initial search process, the auxiliary binding sites further extend the
effective target region and therefore facilitate the target location.
