The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion

Nat Cell Biol. 2009 Mar;11(3):344-9. doi: 10.1038/ncb1843. Epub 2009 Feb 15.


Although many proteins can misfold into a self-seeding amyloid-like conformation, only six are known to be infectious, that is prions. The prions [PSI(+)], [PIN(+)], [URE3], [SWI(+)] and [HET-s] cause distinct heritable physiological changes in fungi, whereas PrP(Sc) causes infectious encephalopathies in mammals. It is unknown whether 'protein-only' inheritance is limited to these exceptional cases or whether it represents a widespread mechanism of epigenetic control. Towards this goal, we now describe a new prion formed by the Cyc8 (Ssn6) protein of Saccharomyces cerevisiae. Analogously to other yeast prions, transient overproduction of a glutamine-rich region of Cyc8 induced a heritable dominant cyc8(-) phenotype that is transmitted cytoplasmically and is dependent on the chaperone Hsp104 and the continued presence of the Cyc8 protein. The evolutionarily conserved Cyc8-Tup1 global transcriptional repressor complex forms one of the largest gene regulatory circuits, controlling the expression of more than 7% of yeast genes. Our finding that Cyc8 can propagate as a prion, together with a recent report that Swi1 of the Swi-Snf global transcriptional regulatory complex also has a prion form, shows that prionization can lead to mass activation or repression of yeast genes and is suggestive of a link between the epigenetic phenomena of chromatin remodelling and prion formation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Fungal*
  • Genes, Dominant
  • Genes, Fungal
  • Heat-Shock Proteins / metabolism
  • Inheritance Patterns / genetics
  • Mutation / genetics
  • Nuclear Proteins / metabolism
  • Phenotype
  • Prions / metabolism*
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic*


  • CYC8 protein, S cerevisiae
  • DNA-Binding Proteins
  • Heat-Shock Proteins
  • Nuclear Proteins
  • Prions
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • TUP1 protein, S cerevisiae
  • HsP104 protein, S cerevisiae