Ontology highlight
ABSTRACT:
PROVIDER: PRJNA872289 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21168729_1.fastq.gz | Fastqsanger.gz | |||
| SRR21168729_2.fastq.gz | Fastqsanger.gz | |||
| SRR21168730_1.fastq.gz | Fastqsanger.gz | |||
| SRR21168730_2.fastq.gz | Fastqsanger.gz | |||
| SRR21168731_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
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:This submission consists of the mass spectrometry raw files for the manuscript by Jin et al. (Mutational analysis of GSK3B protein kinase together with kinome-wide binding and stability studies suggest context-dependent recognition of kinases by the chaperone HSP90). This submission contains files for the data presented as supplementary tables 2 and 3 acquired on an Orbitrap Velos.
2016-01-06 | MSV000079445 | MassIVE
Project description:We report the application of DHS-Seq and digital genomic footprinting to study chromatin changes and transcription factor-DNA binding upon long-term Hsp90 depletion utilizing the temperature-sensitive allele G170D. By generating about 86 and 85.6 million reads for wild type and mutant, we were able to reconstitute the chromatin accessibility and the transcription factor-DNA binding maps under regular conditions and under conditions where Hsp90 was long-term inactivated. We find that there is a global reduction of transcription factor binding sites with concurrent loss of open chromatin upon Hsp90 inactivation. This data was used in conjunction with our previous work involving DHS-Seq studies and short-term Hsp90 depletion (GEO GSE88875) to distinguish the affected transcription factor networks and the chromatin changes upon short- and long-term Hsp90 depletion. We identified two different modes of Hsp90 operation on transcription factor activities – short-term inactivation of Hsp90 altered transcription factor DNA binding activities, whereas long-term Hsp90 inactivation affected the steady-state levels of transcription factors. Overall, this study shows that Hsp90 regulates multiple transcription factor protein families and modulates chromatin architecture on a genome-wide scale.
2019-10-23 | GSE139268 | GEO
Project description:Robustness to perturbation, or canalization, is a fundamental and required feature of complex organisms.1 Mutations are the raw material for evolution, but robustness to their effects is required for organisms to tolerate mutational loads.1 Similarly, robustness to environmental perturbations, or limiting environmental responses to an adaptive range, is necessary for organisms to tolerate environmental variation. Robustness is heritable2-4, but the mechanisms that produce it are poorly understood. Explanations range from the role of specific processes such as heat shock proteins to more general embedded features of developmental systems. Nonlinearities are an embedded, ubiquitous feature of development that may modulate how variation in development relates to phenotypic robustness.5,6 Here, we show that variation in Fibroblast Growth Factor 8 (Fgf8) expression across an allelic series has a nonlinear relationship to phenotypic variation, predicting the magnitude of variation within genotypes. These differences in phenotypic variance are independent of genetic variance and so reflect differential robustness to minor environmental variation. Differences in robustness are not related to differences in the variance of gene expression within genotypes. However, mean gene expression levels do vary across genotypes, particularly in genes downstream to FGF8 signaling. Gene expression changes thus explain the genotype-phenotype curve but not the changes in robustness along the curve. This suggests that mechanisms above the gene-regulatory network are important determinants of robustness. Our results show that nonlinearities in developmental mechanisms can persist from genotype to phenotype to produce variation in robustness between genotypes. This suggests that embedded features of development rather than specific canalizing mechanisms explain robustness. How such features vary among individuals in natural populations and relate to genetic variation more generally are key questions for unravelling the origin and evolvability of this fundamental feature of organismal development.
2017-09-23 | GSE87366 | GEO
Project description:Inhibition of the HSP90 chaperone results in depletion of many signaling proteins that drive tumorigenesis, such as downstream effectors of KRAS, the most commonly mutated human oncogene. As a consequence, several small-molecule HSP90 inhibitors are being evaluated in clinical trials as anticancer agents. To prospectively identify mechanisms through which HSP90-dependent cancer cells evade pharmacologic HSP90 blockade, we generated multiple mutant KRAS-driven cancer cell lines with acquired resistance to the purine-scaffold HSP90 inhibitor PU-H71. All cell lines retained dependence on HSP90 function, as evidenced by sensitivity to short hairpin RNA-mediated suppression of HSP90AA1 or HSP90AB1 (also called HSP90α and HSP90β, respectively), and exhibited two types of genomic alterations that interfere with the effects of PU-H71 on cell viability and proliferation: (i) a Y142N missense mutation in the ATP-binding domain of HSP90α that co-occurred with amplification of the HSP90AA1 locus, (ii) genomic amplification and overexpression of the ABCB1 gene encoding the MDR1 drug efflux pump. In support of a functional role for these alterations, exogenous expression of HSP90α Y142N conferred PU-H71 resistance to HSP90-dependent cells, and pharmacologic MDR1 inhibition with tariquidar or lowering ABCB1 expression restored sensitivity to PU-H71 in ABCB1-amplified cells. Finally, comparison with structurally distinct HSP90 inhibitors currently in clinical development revealed that PU-H71 resistance could be overcome, in part, by ganetespib (also known as STA9090) but not tanespimycin (also known as 17-AAG). Together, these data identify potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies.
2016-12-31 | GSE85733 | GEO
Project description:We report the application of DNase-Seq (adapted from Hesselberth et al., 2009, as described in Zelin et al., 2012) to study the chromatin changes upon short Hsp90 depletion by exploiting temperature-sensitive allele G170D (Nathan and Lindquist, 1995). By generating ~43.6 million reads for wild type and 68.6 million reads for mutant, we were able to reconstitute the hypersensitivity maps under the regular conditions and under the conditions where Hsp90 was heat-inactivated. We find that there is a global reduction of open chromatin upon Hsp90 inactivation, as displayed by the decrease of total DHS size and the DHSs numbers. We also find that loss of Hsp90 leads to the increase of open chromatin at certain locations associated with chromatin remodelers such as RSC. Overall this study shows that short term improper functioning of Hsp90 results in genome-wide chromatin perturbations thereby demonstrating an Hsp90-dependence of chromatin architecture.
2016-11-03 | GSE88875 | GEO
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.
2012-05-15 | GSE31226 | GEO
Project description:Molecular determinants of Hsp90 recognition of Src kinase revealed by deep mutational scanning
| PRJNA902714 | ENA
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