High-Throughput Flow Cytometry Combined with Genetic Analysis Brings New Insights into the Understanding of Chromatin Regulation of Cellular Quiescence

Int J Mol Sci. 2020 Nov 27;21(23):9022. doi: 10.3390/ijms21239022.

Abstract

Cellular quiescence is a reversible differentiation state when cells are changing the gene expression program to reduce metabolic functions and adapt to a new cellular environment. When fission yeast cells are deprived of nitrogen in the absence of any mating partner, cells can reversibly arrest in a differentiated G0-like cellular state, called quiescence. This change is accompanied by a marked alteration of nuclear organization and a global reduction of transcription. Using high-throughput flow cytometry combined with genetic analysis, we describe the results of a comprehensive screen for genes encoding chromatin components and regulators that are required for the entry and the maintenance of cellular quiescence. We show that the histone acetylase and deacetylase complexes, SAGA and Rpd3, have key roles both for G0 entry and survival during quiescence. We reveal a novel function for the Ino80 nucleosome remodeling complex in cellular quiescence. Finally, we demonstrate that components of the MRN complex, Rad3, the nonhomologous end-joining, and nucleotide excision DNA repair pathways are essential for viability in G0.

Keywords: DNA repair; G0; Ino80; Rpd3; SAGA; cellular quiescence; chromatin; fission yeast.

MeSH terms

  • Cell Cycle / genetics*
  • Cell Survival
  • Chromatin / metabolism*
  • Cluster Analysis
  • DNA Repair / genetics
  • Flow Cytometry*
  • High-Throughput Screening Assays*
  • Histones / metabolism
  • Models, Biological
  • Mutation / genetics
  • Nonlinear Dynamics
  • Phenotype
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces / genetics*

Substances

  • Chromatin
  • Histones