A genome-wide comprehensive analysis of nucleosome positioning in yeast

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 arrangement regulates other nuclear processes, such as transcription and DNA repair. Despite strong efforts to study nucleosome positioning using Next Generation Sequencing (NGS) data, the mechanism of their collective arrangement along the gene body remains poorly understood. Here, we classify nucleosome distributions of protein-coding genes in Saccharomyces cerevisiae according to their profile similarity and analyse their differences 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 whilst considering the nucleosome arrangement as a whole. 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 the nucleosome distribution. We reveal that the RSC chromatin remodeler—which is responsible for NDR maintenance—is indispensable for decoupling nucleosome arrangement within the gene from positioning outside, which interfere in rsc8-depleted conditions. Moreover, nucleosome profiles 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.Author summary: In baker's yeast, as in other living organisms, the support of genetic information is tightly packaged and separated from the rest of the cell. Folding is achieved on its lowest level by wrapping the DNA around molecular complexes called nucleosomes. However, the survival of the baker's yeast requires that essential cellular processes access the genetic information protected by nucleosomes. Therefore, the nucleosome arrangement along the genome should modulate the access and use of this information and ultimately the functioning of the cell. Despite strong efforts to study nucleosome profiles, the mechanism of their collective arrangement along the genome remains poorly understood. Here, we tackled this issue by comparing and classifying directly the nucleosome profiles along the genes (genomic regions that are known to support the necessary informations for cell functioning). This drives us to highlight that in baker's yeast the spatial organisation of nucleosomes in genes is different from other genomic regions and this difference is maintained actively by energy consuming factors. We show that the regulation and compartmentalisation of nucleosomal organisation require the concomitant actions of local and global processes.