  Transcription factors (TFs) are proteins that bind to specific sites on the
DNA and regulate gene activity. Identifying where TF molecules bind and how
much time they spend on their target sites is key for understanding
transcriptional regulation. It is usually assumed that the free energy of
binding of a TF to the DNA (the affinity of the site) is highly correlated to
the amount of time the TF remains bound (the occupancy of the site). However,
knowing the binding energy is not sufficient to infer actual binding site
occupancy. This mismatch between the occupancy predicted by the affinity and
the observed occupancy may be caused by various factors, such as TF abundance,
competition between TFs or the arrangement of the sites on the DNA. We
investigated the relationship between the affinity of a TF for a set of binding
sites and their occupancy. In particular, we considered the case of lac
repressor (lacI) in E.coli and performed stochastic simulations of the TF
dynamics on the DNA for various combinations of lacI abundance in competition
with TFs that contribute to macromolecular crowding. Our results showed that
for medium and high affinity sites, TF competition does not play a significant
role in genomic occupancy, except in cases when the abundance of lacI is
significantly increased or when a low-information content PWM was used.
Nevertheless, for medium and low affinity sites, an increase in TF abundance
(for both lacI or other molecules) leads to an increase in occupancy at several
sites. Keywords: facilitated diffusion, Position Weight Matrix, thermodynamic
equilibrium, motif information content, molecular crowding
