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 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.

References in corpus (2)

• Nucleosome-mediated cooperativity between transcription factors
• DNA sequence correlations shape nonspecific transcription factor-DNA binding affinity

Cited by in corpus (4)

• Sequence Heterogeneity Accelerates Protein Search for Targets on DNA
• Genome-wide organization of eukaryotic pre-initiation complex is influenced by nonconsensus protein-DNA binding
• Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays
• Nonspecific Protein-DNA Binding Is Widespread in the Yeast Genome