Eukaryotic cells can acquire reversible 'epimutations' which serve as a bet-hedging strategy enabling organisms to adapt to acute changes in cellular homeostasis. Fission yeast (Schizosaccharomyces pombe) provides an elegant model to study how cells acquire epimutations that are dependent on H3K9 methylation as a response to heterochromatin misregulation. This process leads to adaptive and reversible epimutations that promote fitness and cell survival. Several fundamental questions emerge from these observations: How do cells make the right epigenetic choices that promote fitness? Are the choices that cells make random or targeted? Using an inducible approach to trigger heterochromatin misregulation, we built a temporal map of changes in gene expression prior to cells acquiring an adaptive epimutation. Our inducible approach provides a roadmap of the journey that cells undertake prior to adaptation thus enabling us to capture unexpected sources of cellular stress that control cell fitness and survival. We find surprising connections between cell growth, the initiation of a general stress response and ribosomal RNA transcription. Our results reveal that organisms trigger an adaptive response by sensing differential changes in growth rates that fundamentally depends on ribosome assembly and protein synthesis.
Support or Funding Information NIH R35GM137832 and NSF URoL 1921677
