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Nat Genet. 2008 Apr;40(4):460-5. doi: 10.1038/ng.112. Epub 2008 Mar 23.

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

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

Abstract

SWI/SNF, an evolutionarily conserved ATP-dependent chromatin-remodeling complex, has an important role in transcriptional regulation. In Saccharomyces cerevisiae, SWI/SNF regulates the expression of approximately 6% of total genes through activation or repression. 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 function. 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. [SW+] 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.

PMID:
18362884
[PubMed - indexed for MEDLINE]
PMCID:
PMC2633598
Free PMC Article

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