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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\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    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\u2014which is responsible for NDR maintenance\u2014is indispensable for decoupling nucleosome arrangement within the gene from positioning outside, which interfere in\n                    <jats:italic>rsc8<\/jats:italic>\n                    -depleted conditions. Moreover, nucleosome profiles in\n                    <jats:italic>chd1<\/jats:italic>\n                    \u0394 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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1011799","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T13:33:21Z","timestamp":1706103201000},"page":"e1011799","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["A genome-wide comprehensive analysis of nucleosome positioning in 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