Abstract
SWI/SNF, an evolutionarily conserved ATP-dependent chromatin-remodeling complex, has an important role in transcriptional regulation1. In Saccharomyces cerevisiae, SWI/SNF regulates the expression of ∼6% of total genes through activation or repression2. Swi1, a subunit of SWI/SNF, contains an N-terminal region rich in glutamine and asparagine, a notable feature shared by all characterized yeast prions—a group of unique proteins capable of self-perpetuating changes in conformation and function3. Here we provide evidence that Swi1 can become a prion, [SWI+]. Swi1 aggregates in [SWI+] cells but not in nonprion cells. Cells bearing [SWI+] show a partial loss-of-function phenotype of SWI/SNF. [SWI+] can be eliminated by guanidine hydrochloride treatment, HSP104 deletion or loss of Swi1. Moreover, we show [SWI+] is dominantly and cytoplasmically transmitted. Our findings reveal a novel mechanism of 'protein-only' inheritance that results in modification of chromatin-remodeling and, ultimately, global gene regulation.
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Acknowledgements
The authors thank M. Carlson (Department of Genetics and Development, Columbia University) for the gift of the pLS7 plasmid; B.C. Laurent (Department of Oncological Sciences, Mount Sinai School of Medicine) for the gift of the pLY14 plasmid; S. Lindquist (Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology and Howard Hughes Medical Institute) for the Hsp104 antibody; J. Workman for helpful discussions; E. Crow and G.E. Kim for technical assistance; R. Lawrence, C. Kowalczyk, R. Miller, T. Volpe, C. Long and E. Crow for critical comments and manuscript editing. This work was partially supported by grants from the United States Army (0850-370-R744), the Ellison Medical Foundation and the US National Institutes of Health (R01NS056086) to L.L.
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Du, Z., Park, KW., Yu, H. et al. Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae. Nat Genet 40, 460–465 (2008). https://doi.org/10.1038/ng.112
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DOI: https://doi.org/10.1038/ng.112
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