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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.

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