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GSE63539
Homo sapiens
10 Downloadable Samples
(ffymetrixhumanexon1.0starray[cdf:huex10stv2,corer3,a20071112,ep)
Description
The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a first-in-field approach to target AR expression and function and improve outcomes in CRPC.
Publication Title
GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex.
Sample Metadata Fields
Cell line
View Samples- Danio rerio
- 28 Downloadable Samples
Illumina HiSeq 2500
Description
Forced sustained swimming exercise at optimal speed enhances growth in many fish species, particularly through hypertrophy of the white skeletal muscle. The exact mechanism of this effect has not been resolved yet. To explore the mechanism, we first subjected wild-type zebrafish to an exercise protocol validated for exercise-enhanced growth, and showed that exercised zebrafish, which indeed showed enhanced growth, had higher cortisol levels than the non-exercised controls. A central role was therefore hypothesized for the steroid hormone cortisol acting through the Glucocorticoid receptor (Gr). Second, we subjected wild-type zebrafish and zebrafish with a mutant Gr to exercise at optimal, suboptimal and super-optimal speeds and compared them with non-exercised controls. Exercised zebrafish showed growth enhancement at all speeds, with highest growth at optimal speeds. In the Gr mutant fish, exercise resulted in growth enhancement similar to wild-type zebrafish, indicating that cortisol cannot be considered as a main determinant of exercise-enhanced growth. Finally, the transcriptome of white skeletal muscle tissue was analysed by RNA sequencing. The results of this analysis showed that in the muscle tissue of Gr mutant fish a lower number of genes is regulated by exercise than in wild-type fish (183 versus 351). A cluster of 36 genes was regulated by exercise in both wild-type and mutant fish. In this cluster, genes involved in transcriptional regulation and protein ubiquitination were overrepresented. Since growth was enhanced similarly in both wild-type fish and mutants, these processes may play an important role in exercise-enhanced growth. Overall design: Deep-sequencing transcriptome analysis of white muscle samples derived from wild-type (++) or glucocorticoid receptor (Gr) mutant (--) Danio rerio specimens that were exposed to either a resting (REST) or a swimming (UOPT) regimen: wild-type resting (REST++; n=3), Gr mutant resting (REST--; n=3), wild-type swimming (UOPT++; n=3), Gr mutant swimming (UOPT--; n=3).
Publication Title
Cortisol Acting Through the Glucocorticoid Receptor Is Not Involved in Exercise-Enhanced Growth, But Does Affect the White Skeletal Muscle Transcriptome in Zebrafish (<i>Danio rerio</i>).
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
During sexual dimorphism, the loss of one entire X chromosome in Drosophila males is achieved largely via a broad genome-wide aneuploid effect. Exploring how MSL proteins and two large non coding RNAs (roX1 and roX2) modulate trans-acting aneuploid effect for equality to females, we employ a system biology approach (microarray) to investigate the global aneuploid effect of maleless(mle) mutation by disrupting MSL binding. A large number of the genes (144) that encode a broad spectrum of cellular transport proteins and transcription factors are located in the autosomes of Drosophila melanogaster.
Publication Title
Drosophila maleless gene counteracts X global aneuploid effects in males.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli str. k-12 substr. mg1655
- 12 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Cytochrome oxydases and quinol monooxygenase were removed from the E. coli genome resulting in oxygen-independent physiology
Publication Title
Deletion of genes encoding cytochrome oxidases and quinol monooxygenase blocks the aerobic-anaerobic shift in Escherichia coli K-12 MG1655.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli str. k-12 substr. mg1655
- 8 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The PurR regulon in Escherichia coli K-12 MG1655.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli str. k-12 substr. mg1655
- 8 Downloadable Samples
Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Expression profiling of wild type and purR deletion strains of E. coli K-12 MG1655 under both M9 minimal media and addition of adenine.
Publication Title
The PurR regulon in Escherichia coli K-12 MG1655.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
The simultaneous genotyping of tens of thousands of SNP using SNP microarrays is a very important tool that is revolutionizing genetics and molecular biology. In this work, we present a new application of this technique by using it to assess chromatin immunoprecipitation (CHIP) as a means to assess the multiple genomic locations bound by a protein complex recognized by an antibody. We illustrate the use of this technique with an analysis of the change in histone H4 acetylation, a marker of open chromatin and transcriptionally active genomic regions, which occur during the differentiation of human myoblasts into myotubes. Our results are validated by the observation of a significant correlation between the histone modifications detected and the expression of the nearby genes, as measured by DNA microarrays.
Publication Title
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression was determined for both myotubes and myoblasts using Affymetrix HG-U133 A/B arrays.
Publication Title
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli str. k-12 substr. mg1655
- 6 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
The aim of this study is to investigate the changes of global gene expression in E. coli during a carbon source shift.
Publication Title
Network context and selection in the evolution to enzyme specificity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic myotubes in keeping with a retained genetic/epigenetic defect of insulin action.
Publication Title
p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients.
Sample Metadata Fields
Specimen part
View Samples