A Genome-Wide Comprehensive Analysis of Nucleosome Positioning in Yeast

Abstract

In eukaryotic cells, the one-dimensional DNA molecules need to be tightly packaged into the spatially constraining nucleus. Folding is achieved on its lowest level by wrapping the DNA around nucleosomes. Their positioning regulates other nuclear processes, such as transcription and DNA repair. Despite strong efforts to study nucleosome phasing using Next Generation Sequencing (NGS) data, the mechanism of their collective arrangement along the gene body remains poorly understood. Here, we assess the nucleosome profiles of protein-coding genes in Saccharomyces cerevisiae using functional Principal Component Analysis. By decomposing the NGS signals into their main descriptive functions, we compared wild type and chromatin remodeler-deficient strains, keeping position-specific details preserved. A correlation analysis with other genomic properties, such as gene size and length of the upstream Nucleosome Depleted Region (NDR), identified key factors that influence nucleosome phasing. We reveal that the RSC chromatin remodeler — which is responsible for NDR maintenance — is indispensable for decoupling nucleosome arrangement within the gene from phasing outside, which interfere in rsc8-depleted conditions. Moreover, positioning in chd1Δ strains displayed a clear correlation with RNA polymerase II presence, whereas wild type cells did not indicate a noticeable interdependence. We propose that RSC is pivotal for global nucleosome organisation, whilst Chd1 plays a key role for maintaining local arrangement.