GC content strongly influences the role of poly(dA) in the intrinsic nucleosome positioning in Saccharomyces cerevisiae

The nucleosome is the basic structural element of genomic DNA packaging and plays a role in transcription, replication, and recombination. Poly(dA) tracts are considered major sequence determinants of nucleosome positioning, although their role is not well understood. Here, we show that the homopolymeric character and the low GC content of poly(dA)s play different roles in nucleosome formation. We found that the inherent low GC content of poly(dA) alone can account for the deep and anisotropic nucleosome depletion at structurally and functionally important regions of promoters and origins of replication. We also show that the level of nucleosome occupancy at poly(dA) is strongly related to the local nucleotide background and its high frequency of occurrence in Saccharomyces cerevisiae does not appear merely to be associated with its intrinsic nucleosome‐excluding properties. In addition, we show that the GC content alone can predict more than 60% of the in vitro nucleosome map, providing further evidence that the intrinsic nucleosome positioning is more greatly determined by GC content than poly(dA) stretches. Our results are consistent with a model in which poly(dA) stretches act at two distinct levels: first, by its low GC content, which intrinsically contributes to hinder nucleosome formation, and second, by its contiguous runs of dA that selectively drive the recruitment of non‐histone proteins with structural and functional roles.