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GSE67415
Mus musculus
32 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ebf1 is a transcription factor with documented, and dose dependent, functions in both normal and malignant B-lymphocyte development. In order to understand more about the role of Ebf1 in malignant transformation, we have investigated the impact of reduced functional Ebf1 dose on early B-cell progenitors. Gene expression analysis in loss and gain of function analysis suggested that Ebf1 was involved in the regulation of genes of importance for DNA repair as well as cell survival. Investigation of the level of DNA damage in steady state as well as after induction of DNA damage by UV light supported that pro-B cells lacking one functional allele of Ebf1 display a reduced ability to repair DNA damage. This was correlated to a reduction in expression of Rad51 and combined analysis of published 4C and chromatin Immuno precipitation data suggested that this gene is a direct target for Ebf1. Even though the lack of one allele of Ebf1 did not result in any dramatic increase of tumor formation, we noted a dramatic increase in the formation of pro-B cell leukemia in mice carrying a combined heterozygote mutation in the Ebf1 and Pax5 genes. Even though the tumors were phenotypically similar and stable, we noted a large degree of molecular heterogeneity well in line with a mechanism involving impaired DNA repair. Our data support the idea that Ebf1 controls homologous DNA repair in a dose dependent manner and that this may explain the frequent involvement of Ebf1 in human leukemia
Publication Title
Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of dexamethasone-stimulated A549 lung adenocarcinoma epithelial cells treated with a glucocorticoid response (GR) element (GRE) specific DNA binding polyamide. Polyamide designed to target the sequence 5'-WGWWCW-3' and disrupt GR-mediated gene expression. Effects of the GR antagonist mifepristone also examined.
Publication Title
Repression of DNA-binding dependent glucocorticoid receptor-mediated gene expression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcription mediated by hypoxia inducible factor (HIF-1) contributes to tumor angiogenesis and metastasis but is also involved in the activation of cell-death pathways and normal physiological processes. Given the complexity of HIF-1 signaling it could be advantageous to target a subset of HIF-1 effectors rather than the entire pathway. We compared the genome-wide effects of three molecules that each interfere with the HIF-1-DNA interaction: a polyamide targeted to the hypoxia response element (HRE), siRNA targeted to HIF-1, and echinomycin, a DNA binding natural product with a similar but less specific sequence preference to the polyamide. The polyamide affects a subset of hypoxia-induced genes that are consistent with the binding site preferences of the polyamide. For comparison, siRNA targeted to HIF-1 and echinomycin each affect the expression of nearly every gene induced by hypoxia. Remarkably, the total number of genes affected by either polyamide or HIF-1 siRNA over a range of thresholds is comparable. The data shows how polyamides can be used to affect a subset of a pathway regulated by a transcription factor. In addition, this study offers a unique comparison of three complementary approaches towards exogenous control of endogenous gene expression.
Publication Title
Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Androgen Receptor (AR) is essential for the growth and progression of prostate cancer in both hormone-sensitive and hormone-refractory disease. We have designed a sequence-specific DNA binding polyamide (1) that targets the consensus androgen response element (ARE). This polyamide binds the PSA promoter ARE, inhibits androgen-induced expression of PSA and several other AR-regulated genes in cultured prostate cancer cells, and reduces AR occupancy at the PSA promoter and enhancer. Down-regulation of PSA by this polyamide was comparable to that produced by the synthetic anti-androgen bicalutamide (Casodex) at the same concentration. Genome-wide expression analysis reveals that a similar number of transcripts are affected by treatment with the polyamide and with bicalutamide. Direct inhibition of AR-DNA binding by sequence-specific DNA binding small molecules could offer an alternative approach to antagonizing AR activity. A polyamide (2) that targets a different DNA sequence is included as a control.
Publication Title
Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA-binding polyamide.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Social experience influences multiple behaviors of many animal species, including aggression. Social isolation often increases aggressiveness. To investigater the molecular basis of social influences on aggressiveness, we performed comparative gene expression profiling on heads from 6-day-old, single-housed, more aggressive and group-housed, less aggressive male flies.
Publication Title
A common genetic target for environmental and heritable influences on aggressiveness in Drosophila.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global programme of gene expression to identify TNF-induced genes that are negatively regulated by EHMT1
Publication Title
EHMT1 protein binds to nuclear factor-κB p50 and represses gene expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The inflammatory response plays out over time in a reproducible and organized manner after an initiating stimulus. Here we showed that the genes activated in cultured mouse fibroblasts in response to the proinflammatory cytokine tumor necrosis factorcan be divided roughly into three groups, each with different induction kinetics. Whereas differential transcription is important in determining the grouping of these genes, differential mRNA stability also exerted strong influence in some cases overriding that of transcriptional control elements on the temporal order of gene expression. mRNA transcripts expressed early after TNF stimulation have abundant AU-rich elements in their 3'-untranslated regions whereas those expressed later are contain fewer AU-rich sequences. Thus mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of proinflammatory cytokine-induced gene expression.
Publication Title
The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 77 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
L-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease.
Publication Title
Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 41 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This study explores the impact of lifestyle and environment on gene expression through whole transcriptome profiling of peripheral blood samples in Fijian population (native Melanesians and Indians) living in the rural and urban areas.
Publication Title
Using blood informative transcripts in geographical genomics: impact of lifestyle on gene expression in fijians.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Zea mays
- 39 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
The fungal pathogen Ustilago maydis establishes a biotrophic relationship with its host plant maize. Hallmarks of the disease are large plant tumors in which fungal proliferation occurs. Plants have developed various defense pathways to cope with pathogens. We used microarrays to detail the global programme of gene expression during the infection process of Ustilago maydis in its host plant to get insights into the defense programs and the metabolic reprogramming needed to supply the fungus with nutrients.
Publication Title
Ustilago maydis infection strongly alters organic nitrogen allocation in maize and stimulates productivity of systemic source leaves.
Sample Metadata Fields
Specimen part
View Samples