HSP90/70 chaperones are required for rapid nucleosome removal upon induction of the GAL genes of yeast.

Molecular Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 03/2008; 105(8):2975-80. DOI: 10.1073/pnas.0800053105
Source: PubMed

ABSTRACT Induction of transcription of the GAL genes of yeast by galactose is a multistep process: Galactose frees the activator Gal4 of its inhibitor, Gal80, allowing Gal4 to recruit proteins required to transcribe the GAL genes. Here, we show that deletion of components of either the HSP90 or the HSP70 chaperone machinery delays this induction. This delay remains when the galactose-signaling pathway is bypassed, and it cannot be explained by a chaperone requirement for DNA binding by Gal4. Removal of promoter-bound nucleosomes is delayed in a chaperone mutant, and our findings suggest an involvement of HSP90 and HSP70 in this early step in gene induction.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Molecular chaperones are key components in the maintenance of cellular homeostasis and survival, not only during stress but also under optimal growth conditions. Among the ATP-dependent chaperones, heat shock proteins (Hsp90) proteins play a special role. While Hsp90s can interact with unfolded and misfolded proteins, their main (and in eukaryotic cells essential) function appears to involve interactions with a limited number of protein clients at late steps of maturation or in "alter-native" conformations for regulating their stability and activity. Because Hsp90 clients are hubs of diverse signaling networks and participate in nearly every cellular function, Hsp90s interconnect many regulatory circuits and link them to environmental impacts. The availability and activity of Hsp90 may thus influence complex physiological and pathophysiological processes, such as differentiation, development, aging, cancer, neurodegeneration, and infectious diseases. Furthermore, through homeostatic effects on differentiation and development, Hsp90s act as capacitors of phenotypic evolution. In this review, we discuss recent insights in the structure and chaperone cycle of Hsp90s, the mechanisms underlying Hsp90 binding to clients, and potential reasons why client proteins specifically require the assistance of Hsp90s. Moreover, the current views on Hsp90-cochaperone interactions and regulation of Hsp90 proteins via posttranslational modifications are summarized. The second half of this article is devoted to the role of Hsp90 proteins in health and disease, aging, and evolution.
    Biomolecular concepts 02/2012; 3(1):79-97. DOI:10.1515/bmc.2011.054
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hsp100 family chaperones of microorganisms and plants cooperate with the Hsp70/Hsp40/NEF system to resolubilize and reactivate stress-denatured proteins. In yeast this machinery also promotes propagation of prions by fragmenting prion polymers. We previously showed the bacterial Hsp100 machinery cooperates with the yeast Hsp40 Ydj1 to support yeast thermotolerance and with the yeast Hsp40 Sis1 to propagate [PSI+] prions. Here we find these Hsp40s similarly directed specific activities of the yeast Hsp104-based machinery. By assessing the ability of Ydj1-Sis1 hybrid proteins to complement Ydj1 and Sis1 functions we show their C-terminal substrate-binding domains determined distinctions in these and other cellular functions of Ydj1 and Sis1. We find propagation of [URE3] prions was acutely sensitive to alterations in Sis1 activity, while that of [PIN+] prions was less sensitive than [URE3], but more sensitive than [PSI+]. These findings support the ideas that overexpressing Ydj1 cures [URE3] by competing with Sis1 for interaction with the Hsp104-based disaggregation machine, and that different prions rely differently on activity of this machinery, which can explain the various ways they respond to alterations in chaperone function.
    PLoS Genetics 10/2014; 10(10):e1004720. DOI:10.1371/journal.pgen.1004720 · 8.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The histone-like nucleoid-structuring (H-NS) protein binds to horizontally acquired genes in the bacterium Salmonella enterica serovar Typhimurium, silencing their expression. We now report that overcoming the silencing effects of H-NS imposes a delay in the expression of genes activated by the transcriptional regulator PhoP. We determine that PhoP-activated genes ancestral to Salmonella are expressed before those acquired horizontally. This expression timing reflects the in vivo occupancy of the corresponding promoters by the PhoP protein. These results are surprising because some of these horizontally acquired genes reached higher mRNA levels than ancestral genes expressed earlier and were transcribed from promoters harboring PhoP-binding sites with higher in vitro affinity for the PhoP protein. Our findings challenge the often-made assumption that for genes coregulated by a given transcription factor, early genes are transcribed to higher mRNA levels than those transcribed at later times. Moreover, they provide a singular example of how gene ancestry can impact expression timing.
    mBio 08/2014; 5(5). DOI:10.1128/mBio.01485-14 · 6.88 Impact Factor

Full-text (2 Sources)

Available from
Jan 19, 2015