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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Chromatin Assembly and Disassembly / physiology*
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism*
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Chromosomal Proteins, Non-Histone / physiology*
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Cytoplasm / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Epigenesis, Genetic
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Genes, Dominant
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Guanidine / pharmacology
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism*
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NIMA-Interacting Peptidylprolyl Isomerase
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Peptidylprolyl Isomerase / genetics
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Peptidylprolyl Isomerase / metabolism
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Prions / physiology*
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Saccharomyces cerevisiae Proteins / physiology*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription Factors / physiology*
Substances
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Heat-Shock Proteins
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NIMA-Interacting Peptidylprolyl Isomerase
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Prions
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SNF5 protein, S cerevisiae
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SWI1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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HsP104 protein, S cerevisiae
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ESS1 protein, S cerevisiae
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Peptidylprolyl Isomerase
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Guanidine