[SWI+],the prion formed by the chromatin remodeling factor Swi1,is highly sensitive to alterations in hsp70 chaperone system activity

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. © 2011 hines et al.