Heat-shock protein 90 globally targets paused promoters and regulates environment-induced gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE31226 | GEO | 2012/05/15
SECONDARY ACCESSION(S): PRJNA146069
REPOSITORIES: GEO
Similar Datasets
Project description:In this study we provide evidence that Hsp90 binds chromatin at specific sites close to several TSS in Drosophila S2 cell line. In addition of finding a preference for stalled promoter regions of annotated genes, we uncover many intergenic Hsp90 binding sites coinciding with non-annotated transcription start sites. Interestingly, this set includes promoters for primary transcripts of microRNA genes, thereby expanding the scope of Hsp90 to transcriptional control of many genes. We finally conclude that Hsp90 contacts NelfE and thus regulates pol II pausing. Our Dataset comprises of 1 ChIP-seq sample using chromatin from S2 cells which was immunoprecipitated, using antibodies against Drosophila Hsp90. The two biological replicates are submitted along with the input replicates.
2012-05-14 | E-GEOD-31226 | biostudies-arrayexpress
Project description:The Polycomb group (PcG) and Trithorax group (TrxG) of proteins are required for stable and heritable maintenance of repressed and active gene expression states. Their antagonistic function on gene control, repression for PcG and activity for TrxG, is mediated by binding to chromatin and subsequent epigenetic modification of target loci. Despite our broad knowledge about composition and enzymatic activities of the protein complexes involved, our understanding still lacks important mechanistic detail and a comprehensive view on target genes. In this study, we use an extensive data set of ChIP-seq, RNA-seq, and genome-wide detection of transcription start sites (TSSs) to identify and analyze thousands of binding sites for the PcG proteins and Trithorax from a Drosophila S2 cell line. In addition to finding a preference for stalled promoter regions of annotated genes, we uncover many intergenic PcG-binding sites coinciding with non-annotated transcription start sites. Interestingly, this set includes previously unknown promoters for primary transcripts of microRNA genes, thereby expanding the scope of Polycomb control to non-coding RNAs essential for development, apoptosis and growth. Chromatin from S2 cells was immunoprecipitated using antibodies against Pc, Ph, Psc, Trx-C or H3K4me3. In parallel, we isolated RNA from S2 cells and generated global gene expression profiles by RNA-seq. We also surveyed the Drosophila genome for yet non-annotated transcription start sites (TSSs) using a newly adapted protocol for Illumina sequencing (termed 5M-bM-^@M-^Y-MACE) with RNA isolated from S2 cells and embryos.
2010-12-21 | E-GEOD-24521 | biostudies-arrayexpress
Project description:The Polycomb group (PcG) and Trithorax group (TrxG) of proteins are required for stable and heritable maintenance of repressed and active gene expression states. Their antagonistic function on gene control, repression for PcG and activity for TrxG, is mediated by binding to chromatin and subsequent epigenetic modification of target loci. Despite our broad knowledge about composition and enzymatic activities of the protein complexes involved, our understanding still lacks important mechanistic detail and a comprehensive view on target genes. In this study, we use an extensive data set of ChIP-seq, RNA-seq, and genome-wide detection of transcription start sites (TSSs) to identify and analyze thousands of binding sites for the PcG proteins and Trithorax from a Drosophila S2 cell line. In addition to finding a preference for stalled promoter regions of annotated genes, we uncover many intergenic PcG-binding sites coinciding with non-annotated transcription start sites. Interestingly, this set includes previously unknown promoters for primary transcripts of microRNA genes, thereby expanding the scope of Polycomb control to non-coding RNAs essential for development, apoptosis and growth.
2010-12-21 | GSE24521 | GEO
Project description:Accumulating evidence suggests that HSP90 plays roles in modulation of phenotype in vertebrate development, which is closely involved in adaptation and evolution. In this study, we showed that inhibition of embryonic HSP90 function, either by a chemical inhibitor （radicicol） or low conductivity stress, induced variation of cold tolerance in adult zebrafish.
2019-03-02 | GSE111359 | GEO
Project description:Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding and complex assembly processes. Their role in cytosol has been very well elucidated. Chaperones are also present in the nucleus, a compartment where proteins enter after being fully folded in the cytosol, raising an important question about chaperones function in this compartment. We have performed a systematic analysis of nuclear heat- shock protein 90 to identify regulatory functions of this chaperone in the nucleus. Combining physical and genetic interactomes with a cancer co-expression screen allowed us to define 'core functional interactors' of nuclear HSP90 consisting of five proteins. Using transcriptional studies we identified Host Cell Factor C1 (HCFC1) as a metazoan-specific transcriptional regulator that depends on HSP90 for its stability in the nucleus. We found that HSP90 is required for optimal activity of HCFC1 in transcription. Thus our study provides the first global insight into the function of nuclear HSP90.
2019-11-08 | GSE126151 | GEO
Project description:Folding of stringent clients requires transfer from Hsp70 to Hsp90. The co-chaperone Hop physically connects the chaperone machineries. Here we define its role from the remodeling of Hsp70/40-client complexes to the mechanism of client transfer and the conformational switching from stalled to active client-processing states of Hsp90. We show that Hsp70 together with Hsp40 completely unfolds a stringent client, the glucocorticoid receptor ligand binding domain (GR-LBD) in large assemblies. Hop remodels these for efficient transfer onto Hsp90. As p23 enters, Hsp70 leaves the complex via switching between binding sites in Hop. To proceed to client folding, current concepts assume that Hop dissociates and the co-chaperone p23 stabilizes the Hsp90 closed state. In contrast, we show that p23 directly interacts with Hop, relieves the stalling Hsp90-Hop interaction and closes Hsp90. This reaction allows folding of the client and is thus the key regulatory step for the progression of the chaperone cycle. To study the interaction between the different proteins, especially p23 and the DP2 domain of Hop, we performed crosslinking-MS.
2022-02-24 | PXD027413 | Pride
Project description:The molecular chaperone heat shock protein 90 (HSP90) is thought to buffer genetic variation uncoupling phenotypic outcome from individual genotypes. HSP90 thus acts as an evolutionary capacitor by facilitating an accumulation of natural genetic variation. The molecular mechanism underlying the buffering ability is unclear, and HSP90-contingent genetic variation maps both to coding and non-coding parts of the genome. Our genome-wide data indicate that a compromised chaperoning activity of HSP90 causes derepression of endogenous retroviruses (ERVs) in mouse somatic cells. This results in an upregulation of host genes located in the neighborhood of pre-existing ERVs insertion sites. We provide genetic and biochemical evidence that HSP90 cooperates with KAP1/ SETDB1 histone methyltranferase pathway to repress ERVs. Individual mouse strains have unique integration sites of ERVs in their genomes. Consequently distinct genes are responsive to HSP90 inhibitor in different mouse strains depending on the position of the genes vis-à-vis strain-specific ERV insertion sites. Since ERVs have been exapted to drive novel transcriptional networks during mammalian evolution, HSP90 may have acted as a capacitor by buffering variation caused by ERV in non-coding regions of the genome. Our studies provide the first molecular framework by which HSP90 can mitigate genetic variation in gene-regulatory regions affecting gene expression and phenotypes.
2017-01-30 | GSE87119 | GEO
Project description:The molecular chaperone HSP90 aids the maturation of a diverse but select set of metastable protein clients, many of which are key to a variety of signal transduction pathways. HSP90 function has been best investigated in animal and fungal systems, where inhibition of the chaperone has exceptionally diverse effects, ranging from reversing oncogenic transformation to facilitating the acquisition of drug resistance. Inhibition of HSP90 in the model plant Arabidopsis thaliana uncovers novel morphologies dependent on normally cryptic genetic variation and increases stochastic variation inherent to developmental processes. The biochemical activity of HSP90 is strictly conserved between animals and plants. However, the substrates and pathways dependent on HSP90 in plants are poorly understood. Progress has been impeded by reliance on light-sensitive HSP90 inhibitors due to redundancy in the A. thaliana HSP90 gene family. Here we present phenotypic and genome-wide expression analyses of A. thaliana with constitutively reduced HSP90 levels achieved by RNAi targeting. HSP90 reduction affects a variety of quantitative life-history traits, including flowering time and total seed set, and decreases developmental stability. Further, by quantitative analysis of morphological phenotypes, we demonstrate that HSP90-reduction increases phenotypic diversity in both seedlings and adult plants. Several morphologies are synergistically affected by HSP90 and growth temperature. Genome-wide expression analyses also suggest a central role for HSP90 in the genesis and maintenance of plastic responses. The expression results are substantiated by examination of the response of HSP90-reduced plants to attack by caterpillars of the generalist herbivore Trichoplusia ni. HSP90 reduction potentiates a more robust herbivore defense response. In sum, we propose that HSP90 exerts global effects on the environmental responsiveness of plants to many different stimuli. The comprehensive set of HSP90-reduced lines described here is a vital instrument to further examine the role of HSP90 as a central interface between organism, development, and environment. Keywords: HSP90, mutant comparison
2007-05-31 | GSE7796 | GEO
Project description:Regulated translation initiation has the potential to reshape the proteome, but conditions under which start codon selection is altered remain poorly defined. Here, using global translation initiation site profiling, we reveal widespread changes in start codon selection during the mammalian cell cycle. Low-efficiency initiation sites are preferentially repressed in mitosis, resulting in changes in the relative translation of thousands of annotated proteins, alternative translational isoforms, and uORFs. This increased mitotic translational stringency results from the cytoplasmic release of a nuclear pool of eIF1 upon nuclear envelope breakdown. Increased eIF1-40S ribosome interactions repress suboptimal initiation sites to rewire the mitotic proteome. Selectively depleting the nuclear pool of eIF1 eliminates changes to translational stringency during mitosis, resulting in substantially increased cell death following an extended mitotic delay induced by anti-mitotic chemotherapeutics. Thus, cells globally control translation initiation stringency to alter their physiology with critical roles during the mammalian cell cycle.
2023-12-02 | GSE230189 | GEO
Project description:The molecular chaperone HSP90 aids the maturation of a diverse but select set of metastable protein clients, many of which are key to a variety of signal transduction pathways. HSP90 function has been best investigated in animal and fungal systems, where inhibition of the chaperone has exceptionally diverse effects, ranging from reversing oncogenic transformation to facilitating the acquisition of drug resistance. Inhibition of HSP90 in the model plant Arabidopsis thaliana uncovers novel morphologies dependent on normally cryptic genetic variation and increases stochastic variation inherent to developmental processes. The biochemical activity of HSP90 is strictly conserved between animals and plants. However, the substrates and pathways dependent on HSP90 in plants are poorly understood. Progress has been impeded by reliance on light-sensitive HSP90 inhibitors due to redundancy in the A. thaliana HSP90 gene family. Here we present phenotypic and genome-wide expression analyses of A. thaliana with constitutively reduced HSP90 levels achieved by RNAi targeting. HSP90 reduction affects a variety of quantitative life-history traits, including flowering time and total seed set, and decreases developmental stability. Further, by quantitative analysis of morphological phenotypes, we demonstrate that HSP90-reduction increases phenotypic diversity in both seedlings and adult plants. Several morphologies are synergistically affected by HSP90 and growth temperature. Genome-wide expression analyses also suggest a central role for HSP90 in the genesis and maintenance of plastic responses. The expression results are substantiated by examination of the response of HSP90-reduced plants to attack by caterpillars of the generalist herbivore Trichoplusia ni. HSP90 reduction potentiates a more robust herbivore defense response. In sum, we propose that HSP90 exerts global effects on the environmental responsiveness of plants to many different stimuli. The comprehensive set of HSP90-reduced lines described here is a vital instrument to further examine the role of HSP90 as a central interface between organism, development, and environment. Experiment Overall Design: Three differerent experiments were performed. One experiment included lines RNAi-A1, RNAi-A3, and Control-2, with two biological replicates and one technical replicate per line. The second included lines RNAi-A2, RNAi-B1, RNAi-C1, Control-1, and Control-3, with three biological replicates per line. The third included the three single-isoform T-DNA insertion lines, along with the Col-0 control, with three biological replicates per line. See Sangster et al. "Phenotypic Diversity and Altered Environmental Plasticity in Arabidopsis thaliana with Reduced HSP90 Levels" for details of construct construction and further experimental rationale.
2008-06-15 | E-GEOD-7796 | biostudies-arrayexpress