TY - JOUR
T1 - Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae
AU - Du, Zhiqiang
AU - Park, Kyung Won
AU - Yu, Haijing
AU - Fan, Qing
AU - Li, Liming
N1 - Funding Information:
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.
PY - 2008/4
Y1 - 2008/4
N2 - 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 ∼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. [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.
AB - 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 ∼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. [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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U2 - 10.1038/ng.112
DO - 10.1038/ng.112
M3 - Article
C2 - 18362884
AN - SCOPUS:41349087784
SN - 1061-4036
VL - 40
SP - 460
EP - 465
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -