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

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

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromatin Assembly and Disassembly / physiology*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomal Proteins, Non-Histone / physiology*
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epigenesis, Genetic
  • Genes, Dominant
  • Guanidine / pharmacology
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism
  • Prions / physiology*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Heat-Shock Proteins
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Prions
  • SNF5 protein, S cerevisiae
  • SWI1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • HsP104 protein, S cerevisiae
  • ESS1 protein, S cerevisiae
  • Peptidylprolyl Isomerase
  • Guanidine