The detailed positions of nucleosomes profoundly impact gene regulation and are partly encoded by the genomic DNA sequence. However, less is known about the functional consequences of this encoding. Here, we address this question using a genome-wide map of ∼380,000 yeast nucleosomes that we sequenced in their entirety. Utilizing the high resolution of our map, we refine our understanding of how nucleosome organizations are encoded by the DNA sequence and demonstrate that the genomic sequence is highly predictive of the in vivo nucleosome organization, even across new nucleosome-bound sequences that we isolated from fly and human. We find that Poly(dA:dT) tracts are an important component of these nucleosome positioning signals and that their nucleosome-disfavoring action results in large nucleosome depletion over them and over their flanking regions and enhances the accessibility of transcription factors to their cognate sites. Our results suggest that the yeast genome may utilize these nucleosome positioning signals to regulate gene expression with different transcriptional noise and activation kinetics and DNA replication with different origin efficiency. These distinct functions may be achieved by encoding both relatively closed (nucleosome-covered) chromatin organizations over some factor binding sites, where factors must compete with nucleosomes for DNA access, and relatively open (nucleosome-depleted) organizations over other factor sites, where factors bind without competition.
The detailed positions of nucleosomes along genomes have critical roles in transcriptional regulation. Consequently, it is important to understand the principles that govern the organization of nucleosomes in vivo and the functional consequences of this organization. Here we report on progress in identifying the functional consequences of nucleosome organization, in understanding the way in which nucleosome organization is encoded in the DNA, and in linking the two, by suggesting that distinct transcriptional behaviors are encoded through the genome's intrinsic nucleosome organization. Our results thus provide insight on the broader question of understanding how transcriptional programs are encoded in the DNA sequence. These new insights were enabled by individually sequencing ∼380,000 nucleosomes from yeast in their entirety. Using this map, we refine our previous model for predicting nucleosome positions and demonstrate that our new model predicts nucleosome organizations in yeast with high accuracy and that its nucleosome positioning signals are predictive across eukaryotes. We show that the yeast genome may utilize these nucleosome positioning signals to encode regions with both relatively open (nucleosome-depleted) chromatin organizations and relatively closed (nucleosome-covered) chromatin organizations and that this encoding can partly explain aspects of transcription factor binding, gene expression, transcriptional noise, and DNA replication.