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Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae

Nature Genetics volume 40, pages 460–465 (2008)Cite this article

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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Figure 1: Overexpression of SWI1 but not SNF5 functions as Pin+.
Figure 2: Isolation and characterization of [SWI+] candidates.
Figure 3: [SWI+] can exist independently from [PSI+].
Figure 4: [SWI+] is dominantly and cytoplasmically inherited.
Figure 5: Swi1 but not Snf5 exists in distinct conformational states in [SWI+] and [swi−] cells.
Figure 6: Swi1 is the protein determinant of [SWI+].

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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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  1. Haijing Yu

    Present address: Present address: Key Laboratory of Bioresources Conservation and Utilization and Human Genetics Center, Yunnan University, Kunming, Yunnan 650091, China.,

Authors and Affiliations

  1. Department of Molecular Pharmacology and Biological Chemistry, The Feinberg School of Medicine, Northwestern University, Searle 5-474, 320 East Superior Street, Chicago, 60611, Illinois, USA

    Zhiqiang Du, Kyung-Won Park, Haijing Yu, Qing Fan & Liming Li

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Correspondence to Liming Li.

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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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