Elucidating the regulatory mechanism of Swi1 prion in global transcription and stress responses

Transcriptional regulators are prevalent among identified prions in Saccharomyces cerevisiae, however, it is unclear how prions affect genome-wide transcription. We show here that the prion ([SWI(+)]) and mutant (swi1∆) forms of Swi1, a subunit of the SWI/SNF chromatin-remodeling complex, confer dramatically distinct transcriptomic profiles. In [SWI(+)] cells, genes encoding for 34 transcription factors (TFs) and 24 Swi1-interacting proteins can undergo transcriptional modifications. Several TFs show enhanced aggregation in [SWI(+)] cells. Further analyses suggest that such alterations are key factors in specifying the transcriptomic signatures of [SWI(+)] cells. Interestingly, swi1∆ and [SWI(+)] impose distinct and oftentimes opposite effects on cellular functions. Translation-associated activities, in particular, are significantly reduced in swi1∆ cells. Although both swi1∆ and [SWI(+)] cells are similarly sensitive to thermal, osmotic and drought stresses, harmful, neutral or beneficial effects were observed for a panel of tested chemical stressors. Further analyses suggest that the environmental stress response (ESR) is mechanistically different between swi1∆ and [SWI(+)] cells—stress-inducible ESR (iESR) are repressed by [SWI(+)] but unchanged by swi1∆ while stress-repressible ESR (rESR) are induced by [SWI(+)] but repressed by swi1∆. Our work thus demonstrates primarily gain-of-function outcomes through transcriptomic modifications by [SWI(+)] and highlights a prion-mediated regulation of transcription and phenotypes in yeast.