Survival in Quiescence Requires the Euchromatic Deployment of Clr4/SUV39H by Argonaute-Associated Small RNAs

Mol Cell. 2016 Dec 15;64(6):1088-1101. doi: 10.1016/j.molcel.2016.11.020.

Abstract

Quiescence (G0) is a ubiquitous stress response through which cells enter reversible dormancy, acquiring distinct properties including reduced metabolism, resistance to stress, and long life. G0 entry involves dramatic changes to chromatin and transcription of cells, but the mechanisms coordinating these processes remain poorly understood. Using the fission yeast, here, we track G0-associated chromatin and transcriptional changes temporally and show that as cells enter G0, their survival and global gene expression programs become increasingly dependent on Clr4/SUV39H, the sole histone H3 lysine 9 (H3K9) methyltransferase, and RNAi proteins. Notably, G0 entry results in RNAi-dependent H3K9 methylation of several euchromatic pockets, prior to which Argonaute1-associated small RNAs from these regions emerge. Overall, our data reveal another function for constitutive heterochromatin proteins (the establishment of the global G0 transcriptional program) and suggest that stress-induced alterations in Argonaute-associated sRNAs can target the deployment of transcriptional regulatory proteins to specific sequences.

Keywords: Argonaute; Clr4/Suv39H1; G0; H3K9me; RNAi; Schizosaccharomyces pombe; heterochromatin; nuclear exosome; quiescence; sRNA.

MeSH terms

  • Argonaute Proteins / genetics*
  • Argonaute Proteins / metabolism
  • Binding Sites
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Euchromatin / metabolism*
  • Euchromatin / ultrastructure
  • Gene Expression Regulation, Fungal*
  • Heterochromatin / metabolism
  • Heterochromatin / ultrastructure
  • Histone-Lysine N-Methyltransferase
  • Histones / genetics
  • Histones / metabolism
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Resting Phase, Cell Cycle / genetics
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics*
  • Schizosaccharomyces pombe Proteins / metabolism
  • Transcription, Genetic

Substances

  • Ago1 protein, S pombe
  • Argonaute Proteins
  • Cell Cycle Proteins
  • Euchromatin
  • Heterochromatin
  • Histones
  • RNA, Small Interfering
  • Schizosaccharomyces pombe Proteins
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • clr4 protein, S pombe