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GSE51143
Homo sapiens
8 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bromodomains have emerged as attractive candidates for the development of inhibitors targeting gene transcription. Inhibitors of the bromo-and-extra-terminal (BET) family recently showed promising activity in diverse disease models. However, the pleiotropic nature of BET proteins regulating tissue specific transcription has raised safety concerns and suggested that attempts should be made for domain-specific targeting. Here we report that RVX-208, a compound currently in phase II clinical trials, is a BET bromodomain inhibitor specific for second bromodomains (BD2). Co-crystal structures revealed binding modes of RVX-208 and its synthetic precursor and fluorescent recovery after photobleaching demonstrated that RVX-208 displaces BET proteins from chromatin. However, gene expression data showed that BD2 inhibition only modestly affects BET-dependent gene transcription. Our data demonstrate the feasibility of specific targeting within the BET family resulting in different transcriptional outcomes and highlight the importance of BD1 in transcriptional regulation
Publication Title
RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.
Sample Metadata Fields
Cell line
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- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hyphertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.
Publication Title
The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.
Sample Metadata Fields
No sample metadata fields
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
- 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- 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