Non-Mendelian determinant [ISP+] in yeast is a nuclear-residing prion form of the global transcriptional regulator Sfp1

Four protein-based genetic determinants or prions—[SWI⁺], [MCA], [OCT⁺], and [MOT3⁺]—are recent additions to the list of well-known Saccharomyces cerevisiae prions, [PSI⁺], [URE3], and [PIN⁺]. A rapid expansion of this list may indicate that many yeast proteins can convert into heritable prion forms and underscores a problem of prion input into cellular physiology. Here, we prove that the global transcriptional regulator Sfp1 can become a prion corresponding to the prion-like determinant [ISP⁺] described earlier. We show that SFP1 deletion causes an irreversible [ISP⁺] loss, whereas increased SFP1 expression induces [ISP⁺] appearance. Cells that display the [ISP⁺] phenotype contain the aggregated form of Sfp1. Indeed, these aggregates demonstrate a nuclear location. We also show that the phenotypic manifestation of Sfp1 prionization differs from the manifestation of SFP1 deletion. These properties and others distinguish [ISP⁺] from yeast prions described to date.