Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae.
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.
Du
Zhiqiang
Z
Department of Molecular Pharmacology and Biological Chemistry, The Feinberg School of Medicine, Northwestern University, Searle 5-474, 320 East Superior Street, Chicago, Illinois 60611, USA.
Park
Kyung-Won
KW
Yu
Haijing
H
Fan
Qing
Q
Li
Liming
L
D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005799:Genes, Dominant; D019791:Guanidine / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011328:Prions; C066190:SNF5 protein, S cerevisiae; C078562:SWI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C070972:HsP104 protein, S cerevisiae; C000606845:ESS1 protein, S cerevisiae; D019696:Peptidylprolyl Isomerase; D019791:Guanidine