title: Nonspecific transcription-factor-DNA binding influences nucleosome occupancy in yeast.
abstract: 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 the 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.
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Afek
authors.forename: Itamar
authors.initials: I
authors.lastname: Sela
authors.forename: Noa
authors.initials: N
authors.lastname: Musa-Lempel
authors.forename: David B
authors.initials: DB
authors.lastname: Lukatsky
mesh_terms: D001483:Base Sequence; D004271:DNA, Fungal / Q000378:metabolism*; D005800:Genes, Fungal / Q000235:genetics; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013816:Thermodynamics; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
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