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GSE20160
Mus musculus
55 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Catechol-O-methyltransferase (COMT) is an ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity (Andersen & Skorpen, 2009) and risk for developing psychiatric disorders (Harrison & Tunbridge, 2008). A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure-dependent protein translation (Nackley et al., 2006). However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have pursued a genome-wide approach to examining gene expression in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed. This expression difference was validated with qPCR. A B2-B4 Short Interspersed Element (SINE) was inserted in the 3'UTR of Comt1 in 14 strains that also shared a common haplotype. Experiments using mammalian expression vectors of full-length cDNA clones with and without the SINE element demonstrate that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3'UTR B2-B4 SINE element, regulates Comt1 expression and mouse behavior.
Publication Title
Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Using RNA-seq we identified the gene expression changes in GC B cells from LSD1 wild-type or LSD1-deficient mice immunized with T cell dependent antigens (Sheep Red Blood cells) Overall design: RNA seq of sorted GC B cell populations from 3 littermate mice per genotype (3 wild-type, 3 knockout)
Publication Title
Histone demethylase LSD1 is required for germinal center formation and BCL6-driven lymphomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Clinically significant radiation-induced lung injury (RILI) is associated with significant morbidity and mortality and a common toxicity in patients administered thoracic radiotherapy. While the molecular etiology of RILI is poorly understood, we previously characterized a murine model of RILI in which alterations in lung endothelial barrier integrity surfaced as a potentially important pathobiologic event. In these studies, inhibition of HMG-CoA reductase activity (simvastatin) reduced murine RILI-associated lung inflammation and vascular leak and attenuated radiation-induced dysregulation of sphingolipid metabolic pathway genes identified by genome-wide lung gene expression profiling. In the present study, we test the hypothesis that sphingolipid signaling components serve as important modulators of RILI pathobiology and novel therapeutic targets. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to cumulative sphingosine-1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage (BAL) fluid and lung tissue following 25 Gy exposure (6 weeks). Moreover, genetically-engineered mice with either targeted deletion of SphK1 (SphK1-/-), or with reduced expression of selective members of the S1P receptor family (S1PR1+/-, S1PR2-/-, S1PR3-/-,), exhibited marked susceptibility to RILI-mediated lung inflammation. Finally, we assessed the efficacy of three potent vascular barrier-protective S1P analogues FTY720 (FTY), fTysiponate (fTyS) and SEW-2871 (SEW) in attenuating indices of RILI. The phosphonate analogue, fTyS, and to a lesser degree SEW, exhibited significant attenuation of RILI and RILI-induced gene dysregulation compared to control RILI-challenged mice (6 weeks). In contrast, FTY failed to significantly alter physiologic or genomic changes compared to RILI-challenged controls. Together, these results support the targeting of sphingolipid components as a novel and effective therapeutic strategy in RILI.
Publication Title
Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 30 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Gene expression analysis of 7d-old Arabidopsis seedlings exposed to short term (2 h) hypoxia, long term (9 h) hypoxia, and 1 h reoxygenation after long term (9 h) hypoxia to evaluate the regulation of gene expression at the level of translation.
Publication Title
Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and many of the steps involved in lung-specific metastasis. The involvement of Vav proteins in these processes did not correlate with Rac1 and RhoA activity or cell migration, implying the presence of additional biological programs. Microarray analyses revealed that Vav2 and Vav3 controlled a vast transcriptional program in breast cancer cells through mechanisms that were shared between the two proteins, isoform-specific or synergistic. Furthermore, the abundance of Vav regulated transcripts was modulated by Rac1-dependent and Rac1-independent pathways. This transcriptome encoded therapeutically targetable proteins that played non redundant roles in primary tumorigenesis and lung-specific metastasis, such as integrin-linked kinase (Ilk), the transforming growth factorb family ligand inhibin bA, cyclooxygenase-2, and the epithelial cell adhesion molecule Tacstd2. It also contained gene signatures that predicted disease outcome in breast cancer patients. These results identify possible targets for treating breast cancer and lung metastases and provide a potential diagnostic tool for clinical use.
Publication Title
The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to investigate gene expression changes induced by the inhibition of RRAS2 expression using shRNA techniques to stably knockdown the endogenous transcripts of this GTPase in human MDA-MB-231-Luc cells.
Publication Title
Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease.
Sample Metadata Fields
Cell line
View Samples- Populus tremula x populus alba
- 8 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
Ray cells were enriched from wood samples of poplar (Populus x canescens) by LMPC and transcripts monitored by poplar whole genome microarrays. Results provided insight into molecular processes during the transition from dormancy to flowering in early spring in contrast to the active growth phase in summer.
Publication Title
Poplar wood rays are involved in seasonal remodeling of tree physiology.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Heterochromatin protein 1a (HP1a) is a chromatin associated protein that has been well studied in many model organisms, such as Drosophila, where it is a determining factor for classical heterochromatin. HP1a is associated with the two histone methyltransferases SETDB1 and Su(var)3-9, which mediate H3K9 methylation marks and participate in the establishment and spreading of HP1a enriched chromatin. While HP1a is generally regarded as a factor that represses gene transcription, several reports have linked HP1a binding to active genes, and in some cases, it has been shown to stimulate transcriptional activity. To clarify the function of HP1a in transcription regulation and its association with Su(var)3-9, SETDB1 and the chromosome 4 specific protein POF, we conducted genome-wide expression studies and combined the results with available binding data in Drosophila melanogaster. The results suggested that HP1a has a repressing function on chromosome 4, where it preferentially targets non-ubiquitously expressed genes (NUEGs), and a stimulating function in pericentromeric regions. Further, we showed that the effects of SETDB1 and Su(var)3-9 are similar to HP1a, and on chromosome 4, Su(var)3-9, SETDB1 and HP1a target the same genes. In contrast, transposons are repressed by HP1a and Su(var)3-9 but are un-affected by SETDB1 and POF. In addition, we found that the binding level and expression effects of HP1a are affected by gene length. Our results indicate that genes have adapted to be properly expressed in their local chromatin environment.
Publication Title
HP1a, Su(var)3-9, SETDB1 and POF stimulate or repress gene expression depending on genomic position, gene length and expression pattern in Drosophila melanogaster.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
Study of single and double mutants of the two roX RNAs in D. melanogaster Overall design: Study of single and double mutants of the two roX RNAs in D. melanogaster
Publication Title
RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The aim was to identify genes that were commonly influenced by a siRNA targeting PRKCD in breast cancer cell lines.
Publication Title
Down Regulation of CLDND1 Induces Apoptosis in Breast Cancer Cells.
Sample Metadata Fields
Cell line, Treatment
View Samples