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

Although many proteins can misfold into a self-seeding amyloid-like conformation(1), 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(2-4), whereas PrPSc causes infectious encephalopathies in mammals(5). 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(6) forms one of the largest gene regulatory circuits, controlling the expression of more than 7% of yeast genes(7). 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(4), 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.