Precise genome-wide mapping of single nucleosomes and linkers in vivo

We develop a chemical cleavage method that releases single nucleosome dyad-containing fragments, allowing us to precisely map both single nucleosomes and linkers with high accuracy genome-wide in budding yeast. By comparing nucleosome dyad positioning maps to existing genomic and transcriptomic data, we evaluated the contributions of sequence, transcription, histone H1 and H2A.Z in defining the chromatin landscape. A biophysical model that neglects DNA sequence is presented and shows that steric occlusion suffices to explain the salient features of nucleosome positioning. Our study indicates that steric occlusion, and not DNA sequence, is the most important determinant of genome-wide nucleosome positioning.