1. Center for Comparative Genomics and Bioinformatics,
2. Center for Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA

Correspondence to: B. Franklin Pugh^1,2 Correspondence and requests for materials should be addressed to B.F.P. (Email: bfp2@psu.edu).

Abstract

The nucleosome is the fundamental building block of eukaryotic chromosomes. Access to genetic information encoded in chromosomes is dependent on the position of nucleosomes along the DNA. Alternative locations just a few nucleotides apart can have profound effects on gene expression¹. Yet the nucleosomal context in which chromosomal and gene regulatory elements reside remains ill-defined on a genomic scale. Here we sequence the DNA of 322,000 individual Saccharomyces cerevisiae nucleosomes, containing the histone variant H2A.Z, to provide a comprehensive map of H2A.Z nucleosomes in functionally important regions. With a median 4-base-pair resolution, we identify new and established signatures of nucleosome positioning. A single predominant rotational setting and multiple translational settings are evident. Chromosomal elements, ranging from telomeres to centromeres and transcriptional units, are found to possess characteristic nucleosomal architecture that may be important for their function. Promoter regulatory elements, including transcription factor binding sites and transcriptional start sites, show topological relationships with nucleosomes, such that transcription factor binding sites tend to be rotationally exposed on the nucleosome surface near its border. Transcriptional start sites tended to reside about one helical turn inside the nucleosome border. These findings reveal an intimate relationship between chromatin architecture and the underlying DNA sequence it regulates.

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