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SRP065539
Homo sapiens
9 Downloadable Samples
IlluminaHiSeq2500
Description
Glioblastoma ranks as one of the most lethal human cancers, with no effective therapies. To discover novel therapeutic targets, here we performed parallel in vivo and in vitro RNA interference screens of epigenetic regulators and show that transcription elongation factors are essential for human glioblastoma cell survival in vivo, but not in vitro. Context-specific dependency in vivo is driven by microenvironment-induced global changes in the cancer epigenome. JMJD6, a top in vivo-specific hit, binds at enhancers and correlates with increased transcription of known pause-controlled genes. JMJD6 knockdown in patient-derived glioblastoma cells enhances survival of mice bearing orthotopic tumors. Moreover, elevated levels of JMJD6 alone, as well as transcription elongation factors collectively, informs tumor grade and predicts poor prognosis for patients. Our work provides a rationale for targeting transcription elongation as a therapeutic strategy in glioblastoma and, more broadly, the power of in vivo phenotypic screening to identify therapeutically relevant targets in cancer. Overall design: RNA-seq of primary patient-derived GBM cells grown in in vivo tumor microenvironment or in vitro in serum free cell culture
Publication Title
Transcription elongation factors represent in vivo cancer dependencies in glioblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Here we study the adult functions of the single Drosophila member of this subfamily, DHR78, with the goal of defining its ancestral functions in the absence of genetic redundancy. We show that DHR78 mutants have a shortened lifespan and reduced motility. Mated DHR78 mutant females display reduced triglycerides along with a reduced feeding rate. Transcriptional profiling reveals a major role for DHR78 in promoting the expression of genes that are abundantly expressed in the midgut, suggesting that it contributes to nutrient uptake. We also identify roles for DHR78 in maintaining the expression of genes in the ecdysone and Notch signaling pathways. Overall design: Comparison of the transcriptional profile of DHR78-transheterozygote female mutants in a btl>DHR78 background with genetically matched controls
Publication Title
Adult functions for the Drosophila DHR78 nuclear receptor.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Although SIRT1 plays a central role in maintaining metabolic homeostasis, the molecular mechanisms remain unclear. Here we show that loss of the Drosophila SIRT1 homolog sir2 leads to the progressive onset of diabetic phenotypes, similar to studies of SIRT1 in mice. Sir2 function is both necessary and sufficient in the fat body to maintain peripheral insulin sensitivity. This activity is mediated by the Drosophila HNF4 nuclear receptor, which is deacetylated and stabilized through protein interactions with Sir2. This study demonstrates that the key metabolic activities of SIRT1 have been conserved through evolution and establishes HNF4 as a critical downstream target. Overall design: 4 sir2 mutant, 4 control samples, independent biological replicates
Publication Title
Sir2 Acts through Hepatocyte Nuclear Factor 4 to maintain insulin Signaling and Metabolic Homeostasis in Drosophila.
Sample Metadata Fields
Age, Subject
View Samples- Drosophila melanogaster
- 27 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
This study identifies genes that alter their expression in synchrony with the late third instar and prepupal pulses of 20E.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
This study identifies those genes that are dependent on EcR for their proper regulation at the onset of metamorphosis in Drosophila melanogaster.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
To identify 20E-regulated genes, wandering third instar larvae were dissected and their organs were cultured in the presence of either no hormone, 20E alone, cycloheximide alone, or 20E plus cycloheximide for six hours.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Phenobarbital is a well studied xenobiotic compound. In this study, we describe the genomic responses in fruit flies and examine whether animals mutant for DHR96, an ortholog of xenobiotic nuclear receptors PXR and CAR, plays a role in mediating xenobiotic responses in Drosophila.
Publication Title
The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Transgenerational effects of parental metabolic state have been shown, but the mechanism is still unclear. Here we present transcriptome sequencing data from AKHR heterozygous F1 progeny, either from obese maternal or paternal parents, compared to genetically matched heterozygous controls or to wild-type controls Overall design: 3 AKHR heterozygous samples descended from obese maternal parents, 3 AKHR heterozygous samples descended from obese paternal parents, 3 AKHR heterozygous samples descended from non-obese parents, and 3 wild-type controls, independent biological replicates and independent experimental replicates (1 set of samples from each experimental replicate)
Publication Title
Parental obesity leads to metabolic changes in the F2 generation in <i>Drosophila</i>.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
DHR96 plays a role in regulating xenobiotic responses in Drosophila. Using a gain-of-function approach we test whether DHR96 is sufficient to affect detoxification genes in the absence of a xenobiotic insult.
Publication Title
The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Cancer cells utilize a unique form of aerobic glycolysis, called the Warburg effect, to efficiently produce the macromolecules required for proliferation. Here we show that a metabolic program related to the Warburg effect is used during normal Drosophila development and regulated by the fly ortholog of the Estrogen-Related Receptor (ERR) family of nuclear receptors. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triacylglyceride stores, and elevated levels of circulating sugars. Metabolomic profiling revealed that the pathways affected in these mutants correspond to those used in the Warburg effect. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program supporting the dramatic growth that occurs during larval development. This study suggests that mammalian ERR family members may promote cancer by directing a metabolic state that supports proliferation.
Publication Title
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
Sample Metadata Fields
Specimen part
View Samples