[SWI+], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity

Craig, E. A.; Du, Z.; Higurashi, T.; Li, X.; Li, L.; Hines, Justin K.

[SWI+], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity

Abstract

The yeast prion [SWI+], formed of heritable amyloid aggregates of the Swi1 protein, results in a partial loss of function of the SWI/SNF chromatin-remodeling complex, required for the regulation of a diverse set of genes. Our genetic analysis revealed that [SWI+] propagation is highly dependent upon the action of members of the Hsp70 molecular chaperone system, specifically the Hsp70 Ssa, two of its J-protein co-chaperones, Sis1 and Ydj1, and the nucleotide exchange factors of the Hsp110 family ( Sse1/2). Notably, while all yeast prions tested thus far require Sis1, [SWI+] is the only one known to require the activity of Ydj1, the most abundant J-protein in yeast. The C-terminal region of Ydj1, which contains the client protein interaction domain, is required for [SWI+] propagation. However, Ydj1 is not unique in this regard, as another, closely related J-protein, Apj1, can substitute for it when expressed at a level approaching that of Ydj1. While dependent upon Ydj1 and Sis1 for propagation, [SWI+] is also highly sensitive to overexpression of both J-proteins. However, this increased prion-loss requires only the highly conserved 70 amino acid J-domain, which serves to stimulate the ATPase activity of Hsp70 and thus to stabilize its interaction with client protein. Overexpression of the J-domain from Sis1, Ydj1, or Apj1 is sufficient to destabilize [SWI+]. In addition, [SWI+] is lost upon overexpression of Sse nucleotide exchange factors, which act to destabilize Hsp70's interaction with client proteins. Given the plethora of genes affected by the activity of the SWI/SNF chromatin-remodeling complex, it is possible that this sensitivity of [SWI+] to the activity of Hsp70 chaperone machinery may serve a regulatory role, keeping this prion in an easily-lost, meta-stable state. Such sensitivity may provide a means to reach an optimal balance of phenotypic diversity within a cell population to better adapt to stressful environments.

Title	[SWI+], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity
Creator	Craig, E. A.
	Du, Z.
	Higurashi, T.
	Li, X.
	Li, L.
	Hines, Justin K.
Publisher	PLoS Genetics
Academic Department	Chemistry
Division	Natural Sciences
Organization	Lafayette College
Date Issued	February 2011
Date Available	2014-04-15T20:46:30Z
Type	Article
Language	English
Bibliographic Citation	Hines, J. K., et al. (2011 Feb.) "[SWI+], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity." PLoS Genetics 7 (2): e1001309.
Standard Identifier	DOI 10.1371/journal.pgen.1001309
Standard Identifier	Handle 10385/1446
Permalink	http://hdl.handle.net/10385/1446
Rights Statement	Creative Commons - Attribution
Rights Holders	Craig, E. A.
	Du, Z.
	Higurashi, T.
	Li, X.
	Li, L.
	Hines, Justin K.