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

Although many proteins can misfold into a self-seeding amyloid-like conformation1, only six are known to be infectious, i.e. prions; [PSI(+)], [PIN(+)], [URE3], [SWI(+)] and [HET-s] cause distinct heritable physiological changes in fungi2–4, while PrP(Sc) causes infectious encephalopathies in mammals5. It is unknown if “protein-only” inheritance is limited to these exceptional cases, or 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. Analogous to other yeast prions, transient over-production of a glutamine-rich region of Cyc8 induced a heritable dominant cyc8(−) phenotype that is transmitted cytoplasmically and dependent on the chaperone Hsp104 and the continued presence of the Cyc8 protein. The evolutionarily conserved Cyc8-Tup1 global transcriptional repressor complex6 forms one of the largest gene regulatory circuits, controlling the expression of over 7% of yeast genes7. 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 form4, 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 remodeling and prion formation.