  Quantitative understanding of the principles regulating nucleosome occupancy
on a genome-wide level is a central issue in eukaryotic genomics. Here, we
address this question using budding yeast, Saccharomyces cerevisiae, as a model
organism. We perform a genome-wide computational analysis of nonspecific
transcription factor (TF)-DNA binding free energy landscape, and compare this
landscape with experimentally determined nucleosome binding preferences. We
show that DNA regions with enhanced nonspecific TF-DNA binding are
statistically significantly depleted of nucleosomes. We suggest therefore that
the competition between TFs with histones for nonspecific binding to genomic
sequences might be an important mechanism influencing nucleosome-binding
preferences in vivo. We also predict that poly(dA:dT) and poly(dC:dG) tracts
represent genomic elements with the strongest propensity for nonspecific TF-DNA
binding, thus allowing TFs to outcompete nucleosomes at these elements. Our
results suggest that nonspecific TF-DNA binding might provide a barrier for
statistical positioning of nucleosomes throughout the yeast genome. We predict
that the strength of this barrier increases with the concentration of DNA
binding proteins in a cell. We discuss the connection of the proposed mechanism
with the recently discovered pathway of active nucleosome reconstitution.
