title: The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion.
abstract: 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.
authors.affiliation: Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, Illinois 60607, USA.
authors.forename: Basant K
authors.initials: BK
authors.lastname: Patel
authors.forename: Jackie
authors.initials: J
authors.lastname: Gavin-Smyth
authors.forename: Susan W
authors.initials: SW
authors.lastname: Liebman
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015966:Gene Expression Regulation, Fungal; D005799:Genes, Dominant; D005800:Genes, Fungal; D006360:Heat-Shock Proteins / Q000378:metabolism; D040582:Inheritance Patterns / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011328:Prions / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C065455:CYC8 protein, S cerevisiae; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; D011328:Prions; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; C070972:HsP104 protein, S cerevisiae