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GSE87477
Homo sapiens
16 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Type II testicular germ cell cancers (GCC) are the most frequently diagnosed tumors in young men (20 - 40 years) and are classified as seminoma or non-seminoma. GCCs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas display only incomplete remission or relapse and require novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumor therapy, which interferes with the function of bromodomain and extra-terminal (BET)-proteins. Here, we demonstrate that upon JQ1 doses 250 nM GCC cell lines and Sertoli cells display compromised survival and induction of cell cycle arrest. JQ1 treated GCC cell lines display upregulation of genes indicative for DNA damage and a cellular stress response. Additionally, downregulation of pluripotency factors and induction of mesodermal differentiation was detected. GCCs xenografted in vivo showed a reduction in tumor size, proliferation and angiogenesis when subjected to JQ1 treatment. The combination of JQ1 and the histone deacetylase inhibitor romidepsin further enhanced the apoptotic effect in vitro and in vivo. Thus, we propose that JQ1 alone, or in combination with romidepsin may serve as a novel therapeutic option for GCCs.
Publication Title
The bromodomain inhibitor JQ1 triggers growth arrest and apoptosis in testicular germ cell tumours in vitro and in vivo.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Triticum aestivum
- 35 Downloadable Samples
- Affymetrix Wheat Genome Array (wheat)
Description
Two sets of wheat lines near-isogenic to Lr34 were used to compare gene expression profiles of wheat: 1. with and without Lr34 gene; 2. rust and mock inoculation; 3. distal and basal portion of the flag leaves. The two sets of wheat near-isogenic lines were used to subtract genetic background variations and to enrich Lr34-regulated gene expression profiles. The study is aimed to better understand the mechanisms of the well-known durable leaf rust resistance gene, Lr34, mediated resistance at the transcriptome level.
Publication Title
Gene expression patterns in near isogenic lines for wheat rust resistance gene lr34/yr18.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The H4K16 acetyltransferase MOF plays a crucial role in dosage compensation in Drosophila, but has additional, global functions in gene control. We compared the molecular context and effect of MOF activity in male and female flies combining chromosome-wide mapping and transcriptome studies with analyses of defined reporter loci in transgenic flies. MOF distributes dynamically between two types of complexes, the Dosage Compensation Complex (DCC) and complexes containing MBD-R2, a global facilitator of transcription. These different targeting principles define the distribution of MOF between the X chromosome and autosomes and at transcription units with 5 or 3 enrichment.
Publication Title
The activation potential of MOF is constrained for dosage compensation.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The MOF-containing NSL complex binds to many but not all promoters of active genes and potentially contributes to their proper gene expression. It is currently unknown what determines whether an active gene is bound or not. Here, we provide evidence that the NSL complex primarily targets active promoters of most housekeeping genes. There, it co-localizes with the chromatin remodeler NURF and the histone methyltransferase Trithorax. Moreover, despite binding to most housekeeping genes, the NSL complex regulates only a subset of them, which are depleted for certain insulator binding-proteins and enriched for the core promoter motif Ohler 5. We suggest that the combination of general chromatin factors and core promoter motifs is predictive for whether a housekeeping gene is transcriptionally regulated by the NSL complex.
Publication Title
The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor which has been implicated in the growth and development of breast, pancreatic and colorectal cancers (CRC). In order to identify novel LRH-1-regulated genes in CRC cells, we performed gene expression profiling following siRNA-mediated LRH-1 silencing in the CRC cell line HCT116.
Publication Title
LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor which has been implicated in the growth and development of breast, pancreatic and colorectal cancers (CRC). In order to identify novel LRH-1-regulated genes in CRC cells, we performed gene expression profiling following siRNA-mediated LRH-1 silencing in the CRC cell line HT29.
Publication Title
LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Ascending aortic aneurysms (AscAA) are a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Lineage tracing analysis showed that loss of Notch1 in the SHF reduces the number of SHF-derived smooth muscle cells in the aortic root, and RNA-seq analysis demonstrated distinct in vivo expression patterns between lineage-specific regions of the ascending aorta. Finally, Notch1+/- mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 independently predisposes to AscAA. These findings are the first to demonstrate a SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy. Overall design: To determine why dilation was localized to the aortic root in Notch1.129S6+/- mice, RNA-sequencing was performed on proximal and distal ascending aortic tissue from Notch1.129S6+/- mice and wildtype littermates at 2 months of age. Transcriptome analysis was utilized to better understand why the dilation was localized to the aortic root. Hierarchical cluster analysis grouped these samples based on location first and then genotype, and showed that cells of the proximal and distal ascending aorta have distinct gene expression patterns in vivo.
Publication Title
Notch1 haploinsufficiency causes ascending aortic aneurysms in mice.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Bile acids are steroid compounds from the digestive tracts of vertebrates that enter agricultural environments in unusual high amounts with manure. Bacteria degrading bile acids can readily be isolated from soils and waters including agricultural areas. Under laboratory conditions, these bacteria transiently release steroid compounds as degradation intermediates into the environment. These compounds include androstadienediones (ADDs), which are C19-steroids with potential hormonal effects. Experiments with Caenorhabditis elegans showed that ADDs derived from bacterial bile acid degradation had effects on its tactile response, reproduction rate, and developmental speed. Additional experiments with a deletion mutant as well as transcriptomic analyses revealed that these effects might be conveyed by the putative testosterone receptor NHR-69. Soil microcosms showed that the natural microflora of agricultural soil is readily induced for bile acid degradation accompanied by the transient release of steroid intermediates. Establishment of a model system with a Pseudomonas strain and C. elegans in sand microcosms indicated transient release of ADDs during the course of bile acid degradation and negative effects on the reproduction rate of the nematode. This proof-of-principle study points at bacterial degradation of manure-derived bile acids as a potential and so-far overlooked risk for invertebrates in agricultural soils. Overall design: Two strains (N2 Bristol variety; nhr-69 deletion mutant, nhr-69(ok1926) I); two experimental conditions (control/test conditions: without/with 5 µM of the ADD 7a-HADD); 2-3 biological replicates per experimental condition; four contrasts between test and control conditions or strains functionally analyzed. Please note that differential gene expression data calculated between samples, as indicated in the processed data file names, is provided as Series supplementary file.
Publication Title
Steroids originating from bacterial bile acid degradation affect Caenorhabditis elegans and indicate potential risks for the fauna of manured soils.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples