Regulation of the Hsf1-dependent transcriptome via conserved bipartite contacts with Hsp70 promotes survival in yeast
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ABSTRACT:
PROVIDER: PRJNA532914 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8902390_1.fastq.gz | Fastqsanger.gz | |||
| SRR8902390_2.fastq.gz | Fastqsanger.gz | |||
| SRR8902400_1.fastq.gz | Fastqsanger.gz | |||
| SRR8902400_2.fastq.gz | Fastqsanger.gz | |||
| SRR8902391_1.fastq.gz | Fastqsanger.gz |
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Project description:Protein homeostasis and cellular fitness in the presence of proteotoxic stress is promoted by heat shock factor 1 (HSF1), which controls basal and stress-induced expression of molecular chaperones and other targets. The major heat shock proteins Hsp70 and Hsp90 in turn participate in a negative feedback loop that ensures appropriate coordination of the heat shock response with environmental conditions. Features of this regulatory circuit in the budding yeast Saccharomyces cerevisiae have been recently defined, most notably regarding direct interaction between Hsf1 and the constitutively expressed Hsp70 Ssa1. We sought to further explore the complex nature of Ssa1/Hsf1 regulation. Ssa1 is found to interact independently with both the previously defined CE2 site in the Hsf1 carboxyl-terminal transcriptional activation domain as well as a novel site that we identify within the amino-terminal activation domain. Consistent with both sites bearing a recognition signature for Hsp70, we demonstrate that Ssa1 contacts Hsf1 using its substrate binding domain and abolishing either regulatory site results in loss of Ssa1 association. Removing Hsp70 regulation of Hsf1 results in global dysregulation of Hsf1 transcriptional activity, with synergistic effects when both sites are disrupted together on both gene expression and cellular fitness. Finally, we find that Hsp70 interacts with both transcriptional activation domains of Hsf1 in the related yeast Lachancea kluyveri, implying a conserved mechanism of regulation to promote cellular proteostasis.
2019-04-16 | GSE129832 | GEO
Project description:Protein homeostasis and cellular fitness in the presence of proteotoxic stress is promoted by heat shock factor 1 (Hsf1), which controls basal and stress-induced expression of molecular chaperones and other targets. The major heat shock proteins and molecular chaperones Hsp70 and Hsp90, in turn, participate in a negative feedback loop that ensures appropriate coordination of the heat shock response with environmental conditions. Features of this regulatory circuit in the budding yeast Saccharomyces cerevisiae have been recently defined, most notably regarding direct interaction between Hsf1 and the constitutively expressed Hsp70 protein Ssa1. Here, we sought to further examine the Ssa1/Hsf1 regulation. We found that Ssa1 interacts independently with both the previously defined CE2 site in the Hsf1 C-terminal transcriptional activation domain and with an additional site that we identified within the N-terminal activation domain. Consistent with both sites bearing a recognition signature for Hsp70, we demonstrate that Ssa1 contacts Hsf1 via its substrate-binding domain and that abolishing either regulatory site results in loss of Ssa1 interaction. Removing Hsp70 regulation of Hsf1 globally dysregulated Hsf1 transcriptional activity, with synergistic effects on both gene expression and cellular fitness when both sites are disrupted together. Finally, we report that Hsp70 interacts with both transcriptional activation domains of Hsf1 in the related yeast Lachancea kluyveri Our findings indicate that Hsf1 transcriptional activity is tightly regulated to ensure cellular fitness and that a general and conserved Hsp70-HSF1 feedback loop regulates cellular proteostasis in yeast.
| S-EPMC6690698 | biostudies-literature
Project description:Heat Shock Factor 1 (HSF1) is best known as the master transcriptional regulator of the heat-shock response (HSR), a conserved adaptive mechanism critical for protein homeostasis (proteostasis). Combining a genome-wide RNAi library with an HSR reporter, we identified JMJD6 as an essential mediator of HSF1 activity. In follow-up studies, we found that JMJD6 is itself a non-canonical transcriptional target of HSF1 which acts as a critical regulator of proteostasis. In a positive feedback circuit, HSF1 binds and promotes JMJD6 expression, which in turn reduces HSP70 R469 monomethylation to disrupt HSP70-HSF1 repressive complexes resulting in enhanced HSF1 activation. Thus, JMJD6 is intricately wired into the proteostasis network where it plays a critical role for cellular adaptation to proteotoxic stress.
2024-07-18 | GSE270672 | GEO
Project description:Heat Shock Factor 1 (HSF1) is best known as the master transcriptional regulator of the heat-shock response (HSR), a conserved adaptive mechanism critical for protein homeostasis (proteostasis). Combining a genome-wide RNAi library with an HSR reporter, we identified JMJD6 as an essential mediator of HSF1 activity. In follow-up studies, we found that JMJD6 is itself a non-canonical transcriptional target of HSF1 which acts as a critical regulator of proteostasis. In a positive feedback circuit, HSF1 binds and promotes JMJD6 expression, which in turn reduces HSP70 R469 monomethylation to disrupt HSP70-HSF1 repressive complexes resulting in enhanced HSF1 activation. Thus, JMJD6 is intricately wired into the proteostasis network where it plays a critical role for cellular adaptation to proteotoxic stress.
2024-07-18 | GSE270671 | GEO
Project description:The Pacific oyster Crassostrea gigas, a commercially important species inhabiting the intertidal zone, can tolerate temperature fluctuations. Heat shock transcription factor 1 (HSF1) plays an important role in the process of resistance of thermal stress. However, HSF1 has not been fully characterized in the Pacific oyster. C. gigas with an expansion of heat shock protein (HSP) 70. In this study, we analyzed genes regulated by HSF1 in response to heat shock by Chromatin immunoprecipitation followed sequencing (ChIP-seq), determined the expression patterns of target genes by qRT-PCR, and validated the regulatory relationship between one HSP70 and HSF1. We found 916 peaks corresponding to specific binding sites of HSF1, and peaks were annotated to nearest genes. In Gene Ontology analysis, HSF1 target genes was related to signal transduction, energy production, and response to biotic stimulus. Four HSP70 genes, two HSP40 genes, and one small HSP gene exhibited binding to HSF1. One HSP70 with a binding site in the promoter region was validated to be regulated by HSF1 under heat shock. These results provide a basis for future studies aimed at determining the mechanisms underlying thermal tolerance and provide insights into gene regulation in the Pacific oyster.
2020-10-16 | GSE138959 | GEO
Project description:Transcription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access have not been well known in mammalian cells. We show a physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed conditions, and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads preloading of RNA polymerase II and opens chromatin structure by recruiting a histone chaperone FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanistic basis for constitutive HSF1 access to nucleosomal DNA, which is important for both basal and inducible gene expression. To examine whether the HSF1-RPA complex regulates the expression of genes, mRNA levels in MEFs with/without HSF1- or RPA1-shRNA were analyzed by DNA microarray analysis using GeneChip Mouse Gene 1.0 ST Arrays (Affymetrix).
2012-12-31 | E-GEOD-38412 | biostudies-arrayexpress
Project description:Transcription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access have not been well known in mammalian cells. We show a physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed conditions, and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads preloading of RNA polymerase II and opens chromatin structure by recruiting a histone chaperone FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanistic basis for constitutive HSF1 access to nucleosomal DNA, which is important for both basal and inducible gene expression.
2012-12-31 | GSE38412 | GEO
Project description:The heat shock response is a universal transcriptional response to proteotoxic stress orchestrated by heat shock transcription factor Hsf1 in all eukaryotic cells. Despite over 40 years of intense research, the mechanism of HSF1 activity regulation remains poorly understood at a molecular level. In metazoa Hsf1 trimerizes upon heat shock through a leucin-zipper domain and binds to DNA. How Hsf1 is dislodged from DNA and monomerized remained enigmatic. Here, using purified proteins we demonstrate that unmodified trimeric Hsf1 is dissociated from DNA in vitro by Hsc70 and DnaJB1. Hsc70 binds to multiple sites in Hsf1 with different affinities. Hsf1 trimers are monomerized by successive cycles of entropic pulling, unzipping the triple leucinezipper. Starting this unzipping at several protomers of the Hsf1 trimer results in faster monomerization. This process directly monitors the concentration of Hsc70 and DnaJB1. During heat shock adaptation Hsc70 first binds to a high affinity site in the transactivation domain leading to partial attenuation of the response and subsequently, at higher concentrations, Hsc70 removes Hsf1 from DNA to restore the resting state.
2020-06-22 | PXD017406 | Pride
Project description:The cells with the impaired Hsp40/Hsp70 chaperone complex Mas5/Ssa2 exhibit a transriptional response that is simillar to that of cells with the elevated levels of the heat-shock factor 1 (Hsf1) or heat-stressed wild type fission yeast cells
2013-09-20 | GSE50156 | GEO
Project description:Upon heat shock, Hsf1 protein is extensively phosphorylated, however, this modification is inhibited by an hsf1-bal mutation. To get genome-wide effect of the hyperphosphorylation on Hsf1-regulated transcription, the heat-induced gene expression profiles in HSF1 and hsf1-bal cells were compared. Keywords: stress response
2005-09-27 | GSE3361 | GEO