A genome-wide comprehensive analysis of nucleosome positioning in yeast

PLoS Comput Biol. 2024 Jan 24;20(1):e1011799. doi: 10.1371/journal.pcbi.1011799. eCollection 2024 Jan.

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 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.

MeSH terms

  • Chromatin Assembly and Disassembly / genetics
  • DNA
  • Nucleosomes / genetics
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • RNA Polymerase II
  • DNA

Grants and funding

This work was supported by Fondation ARC [PGA1 RF20170205342]; Comité Ile-de-France - La Ligue Nationale Contre le Cancer. K.A. was supported by a PhD training contact from the French Ministry of Higher Education and Research. L.Z. was supported by a PhD training contract from the CEA NUMERICS program, which has received funding from European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 800945. This project has received financial support from the CNRS through the MITI interdisciplinary programs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.