Reference: Patel BK, et al. (2009) The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion. Nat Cell Biol 11(3):344-9

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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.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Patel BK, Gavin-Smyth J, Liebman SW
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