  Recent genome-wide measurements of binding preferences of ~200 transcription
regulators in the vicinity of transcription start sites in yeast, have provided
a unique insight into the cis- regulatory code of a eukaryotic genome (Venters
et al., Mol. Cell 41, 480 (2011)). Here, we show that nonspecific transcription
factor (TF)-DNA binding significantly influences binding preferences of the
majority of transcription regulators in promoter regions of the yeast genome.
We show that promoters of SAGA-dominated and TFIID-dominated genes can be
statistically distinguished based on the landscape of nonspecific protein-DNA
binding free energy. In particular, we predict that promoters of SAGA-dominated
genes possess wider regions of reduced free energy compared to promoters of
TFIID-dominated genes. We also show that specific and nonspecific TF-DNA
binding are functionally linked and cooperatively influence gene expression in
yeast. Our results suggest that nonspecific TF-DNA binding is intrinsically
encoded into the yeast genome, and it may play a more important role in
transcriptional regulation than previously thought.
