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Mus musculus
16 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
The MYB oncogene is widely expressed in acute leukemias and is important for the continued proliferation of leukemia cells, raising the possibility that MYB may be a therapeutic target. However realization of this potential requires (i) a significant therapeutic window for MYB inhibition, given its essential role in normal hematopoiesis; and (ii) an approach for developing an effective therapeutic. We previously showed that the interaction of Myb with the coactivator CBP/p300 is essential for its transforming activity. Here we use hematopoietic cells from the Booreana mouse strain, which carries a mutation in Myb that prevents interaction with CBP/p300, to examine the requirement for this interaction in myeloid transformation and leukemogenesis. Using this strain and a strain (plt6) carrying a complementary mutation in p300, we show that the Myb-p300 interaction is essential for in vitro transformation by the myeloid leukemia oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9. We further show that unlike cells from wild-type (WT) mice, Booreana cells fail to induce leukemia upon transplantation into irradiated recipients following transduction with an AML1-ETO9a retrovirus. These data highlight disruption of the Myb-p300 interaction as a potential therapeutic strategy for AML and suggest that such a strategy would have a useable therapeutic index since Booreana mice, unlike Myb null mice, are viable. Finally we have begun to explore the molecular basis of the these observations by gene expression profiling; this highlighted several genes previously implicated in myeloid leukemogenesis as being differentially expressed between WT and Booreana cells transduced with AML1-ETO9a.
Publication Title
Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes.
Sample Metadata Fields
Specimen part
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GSE4737- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Summary:
Publication Title
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples GSE2555- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)
Description
HEK293 cells were transfected with control plasmid (pcDNAI/Neo;Invitrogen) or with the plasmid encoding HCaRG. Stable transfectants were synchronized and grown in the presence of 10% FBS for 48 h. Total RNAs were purified with the mini RNeasy kit (Qiagen).
Publication Title
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1.
Publication Title
SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Drosophila Gene 1.1 ST Array (drogene11st)
Description
The Drosophila TRIM-NHL protein Brain tumor (Brat) plays important roles during early embryogenesis, in cell fate decisions, during neurogenesis and in mature neurons. Brat is an RNA-binding protein and functions as translational repressor. However, which RNAs Brat regulates and how RNA-binding specificity is achieved, is unknown. Using RNA-Immunoprecipitation we identify Brat-bound mRNAs in Drosophila embryos and define a consensus binding motif.
Publication Title
The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
Background Alternative splicing (AS) is a central mechanism of genetic regulation which modifies the sequence of RNA transcripts in higher eukaryotes. AS has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mRNAs. Results In the present study, alterations to the global RNA splicing landscape of cellular genes upon viral infection were investigated through high-throughput RNA sequencing (RNA-seq) studies using mammalian reovirus as a model. Our study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in eukaryotic cells following infection with a human virus. We identify modifications in the AS patterns of 240 cellular transcripts frequently involved in the regulation of gene expression and RNA metabolism. A significant number of the modified transcripts are also encoded by genes with important roles in viral infection/immunity. These modifications are expected to alter the functions of many cellular proteins. Finally, we used RT-PCR analysis in order to experimentally validate differential modifications in alternative splicing patterns that were observed through RNA-seq studies. Conclusion The present study demonstrated that viral infection can extensively modify the splicing patterns of numerous cellular transcripts. These findings provide additional insights into the complexity of virus-host interactions as these splice variants expand proteome diversity and function during viral infection. Finally, these data open new avenues of research for a better understanding of post-transcriptional events during virus infection and possible new targets toward the development of antiviral agents. Overall design: mRNAs were isolated from L929 mouse cell line, 14 hours after infection with T3D-S Reovirus or T3D-S Mutant reovirus at a MOI of 50. Control cells were uninfected. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq. Gene expression and alternative splicing were caracterized using Bowtie and RSEM.
Publication Title
Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus-Host Interactions.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Foxl2 is a forkhead transcription factor expressed only in the female, but not in the male gonad. We have created mice homozygous mutant for the Foxl2 gene (KO) as well as mice carrying a conditional mutant Foxl2 allele (floxed).
Publication Title
Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Steroid hormones regulate essential physiological processes and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by LH via its receptor leading to increased cAMP production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Leydig cell steroidogenesis then passively decreases following the rapid degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutive steroidogenic cell line R2C. Our data identify AMPK as an active repressor of steroid hormone biosynthesis in steroidogenic cells that is essential to preserve cellular energy and prevent excess steroid production.
Publication Title
A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Phytochromes are red/far red photosensors regulating numerous developmental programs in plants. Among them phytochrome A (phyA) is essential to enable seedling de-etiolation in continuous far-red (FR) light a condition mimicking the environment under a dense canopy. The ecological relevance of this response is demonstrated by the high mortality rate of phyA mutants germinating in deep vegetational shade. phyA signaling involves a direct interaction of the photoreceptor with members of the bHLH transcription factor family, PIF1 and PIF3 (Phytochrome Interacting Factor). Here we investigated the involvement of PIF4 and PIF5 in phyA signaling and found that they redundantly control de-etiolation in FR light. The pif4pif5 double mutant is hypersensitive to low fluence rates of FR light. This phenotype is dependent on FR light perception by phyA but does not rely on alterations of the phyA level. Our microarrays analysis shows that PIF4 and PIF5 are part of an inhibitory mechanism repressing the expression of some light-responsive genes in the dark and are also needed for full expression of several growth-related genes in the light. Unlike PIF1 and PIF3, PIF4 and PIF5 are not degraded in response to FR light indicating that they are light-regulated by a different mechanism. Our genetic analysis suggests that this is achieved through the sequestration of these PIFs by the closely related bHLH transcription factor HFR1 (long Hypocotyl in FR light).
Publication Title
Phytochrome interacting factors 4 and 5 redundantly limit seedling de-etiolation in continuous far-red light.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 13 Downloadable Samples
- Porcine Gene 1.1 ST Array (porgene11st)
Description
The stomach is often considered a single compartment, but morphological differences among different areas are well known. Oxyntic mucosa (OXY) is primarily equipped for acid secretion, while it is not enough clear if gastric functional control are shared with other areas.
Publication Title
Differential gene expression in the oxyntic and pyloric mucosa of the young pig.
Sample Metadata Fields
Sex, Specimen part
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