4.8 Article

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

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NATURE GENETICS
卷 40, 期 4, 页码 460-465

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NATURE PUBLISHING GROUP
DOI: 10.1038/ng.112

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  1. NINDS NIH HHS [R01 NS056086-01A2, R01NS056086, R01 NS056086] Funding Source: Medline

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SWI/SNF, an evolutionarily conserved ATP-dependent chromatin-remodeling complex, has an important role in transcriptional regulation(1). In Saccharomyces cerevisiae, SWI/SNF regulates the expression of similar to 6% of total genes through activation or repression(2). 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(3). 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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