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SRP021058
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
The goal of this study was to determine the effects of dietary selenium levels on translational control of selenoprotein synthesis in mouse liver. Overall design: Wild type mice and mice expressing a mutant Sec-tRNA gene (TrspA37G) were fed diets supplemented with 0, 0.1, or 2 ppm selenium for 6 weeks. Livers were harvested and ribosome and mRNA profiles were generated by deep-sequencing using the Illumina HiSeq 2000.
Publication Title
Translational redefinition of UGA codons is regulated by selenium availability.
Sample Metadata Fields
Age, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 99 Downloadable Samples
- Illumina HiSeq 2000
Description
The circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin stimulated glucose uptake were significantly reduced upon CLOCK depletion. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans. Overall design: 100 samples from 2 donors. Together with GSE108539, part of the same study described above.
Publication Title
Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This present study is the first to investigate the global changes in host gene expression during the interaction of human bronchial epithelial cells and live Alternaria spores. Human bronchial epithelial cells (BEAS2-B) were exposed to spores or media alone for 24 hours. RNA was collected from three biological replicates/treatment and used to assess changes in gene expression patterns using Affymetrix Human Genome U133 Plus 2.0 Arrays. Interestingly, many cytokine/chemokine immune response genes were upregulated. Genes involved in cell death, retinoic acid signaling, TLR3, and interferon response pathways were also significantly upregulated.
Publication Title
Analysis of global gene expression changes in human bronchial epithelial cells exposed to spores of the allergenic fungus, Alternaria alternata.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Short-term bed rest is used to simulate muscle disuse in humans. In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects. Identifying muscle transcriptional events in response to bed rest and age-related differences will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations. Skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aide in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse. Short-term muscle disuse is also characterized by skeletal muscle insulin resistance, though this response is divergent across subjects. The mechanisms regulating inactivity-induced insulin resistance between populations that are more or less susceptible to disuse-induced insulin resistance are not known, and delineated by age. High Susceptibility participants were uniquely characterized with muscle gene responses described by a decrease in pathways responsible for lipid uptake and oxidation, decreased capacity for triglyceride export (APOB), increased lipogenesis (i.e., PFKFB3, FASN), and increased amino acid export (SLC43A1). Overall design: RNA was isolated and sequenced from muscle biopsies obtained from the vastus lateralis of YOUNG (N=9) and OLD (N=18) men and women before and after five days of bed rest. Sequencing libraries (18 pM) were chemically denatured and applied to an Illumina TruSeq v3 single read flowcell using an Illumina cBot. Hybridized molecules were clonally amplified and annealed to sequencing primers with reagents from an Illumina TruSeq SR Cluster Kit v3-cBot-HS (GD-401-3001). Following transfer of the flowcell to an Illumina HiSeq 2500 instrument (HCS v2.0.12 and RTA v1.17.21.3), a 50 cycle single read sequence run was performed using TruSeq SBS v3 sequencing reagents (FC-401-3002). The design formula was constructed by following the section on group-specific condition effects, individuals nested within groups in the DESeq2 vignette. The design included age + age:nested + age:time to test for differences in bed rest in old subjects, young subjects and the interaction, in this case if bed rest effects are different between the two age groups (where age is young or old, nested is patient number nested by age and time is pre- or post-bed rest). A similar design was used to determine susceptibility to disuse-induced insulin resistance, where “susceptibility” took the place of “age”.
Publication Title
Disuse-induced insulin resistance susceptibility coincides with a dysregulated skeletal muscle metabolic transcriptome.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Drosophila melanogaster
- 38 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (FruM). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. By over-expressing individual FruM isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional response by RNA-sequencing, we show that three FruM isoforms have different regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of FruM isoforms. Overall design: RNA seqeuncing was performed on mRNA derived from adult male or female heads, for a total of 39 samples. These samples included two wild type genotypes (Berlin and Canton-S), two transheterozygous mutants for fru P1 (Df(3R)P14/Df(3R)fru4-40 and fruw12/ Df(3R)ChaM5), and 3 overexpressing genotypes (fru P1-Gal4: UAS-FruMA, UAS-FruMB, UAS-FruMC). There were at least 3 replicates from biological samples for all sex by genotype combinations.
Publication Title
Sex Differences in Drosophila Somatic Gene Expression: Variation and Regulation by doublesex.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3-UTR regulatory BAT (TGF activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts.
Publication Title
Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice were fed Se-deficient or Se-adequate diets for 6 weeks. Liver and lung tissue were harvested and processed for RNA-Seq, ribosome profiling, and microarray analysis. From these studies, we identified changes in mRNA levels and translation of selenoprotein genes and genes regulated by interferon-gamma. Cytokine profiles of serum indicated that interferon-gamma and IL-6 levels were increased in the Se-adequate mice relative to Se-deficient mice.
Publication Title
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify transcriptional targets altered in the embryonic heart after exposure to TCE, and possible protective effects of folate, we used DNA microarray technology to profile gene expression in embryonic mouse hearts with maternal TCE exposure and dietary changes in maternal folate. Results: Exposure to low doses of TCE (10ppb) caused extensive alterations in transcripts encoding proteins involved in transport, ion channel, transcription, differentiation, cytoskeleton, cell cycle and apoptosis. Exogenous folate did not offset the effects of TCE exposure on normal gene expression and both high and low levels of folate produced additional significant changes in gene expression. Conclusions: A mechanism where TCE induces a folate deficiency does not explain altered gene expression patterns in the embryonic mouse heart. The data further suggest that use of folate supplementation, in the presence of this toxin, may be detrimental and non-protective of the developing embryo.
Publication Title
Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We previously identified the ZTRE in genes involved in zinc homeostasis and showed that it mediates transcriptional repression in response to zinc. We now report that ZNF658 acts at the ZTRE. ZNF658 was identified by MALDI-TOF mass spectrometry of a band excised after EMSA using a ZTRE probe. The protein contains a KRAB domain and 21 zinc fingers. It has similarity with ZAP1 from Saccharomyces cerevisiae, which regulates the response to zinc restriction, including a conserved DNA binding region we show to be functional also in ZNF658. siRNA targeted to ZNF658 abrogated the zinc-induced, ZTRE-dependent reduction in SLC30A5 (ZnT5), SLC30A10 (ZnT10) and CBWD transcripts in human Caco-2 cells and the ability of zinc to repress reporter gene expression from corresponding promoter-reporter constructs. Microarray analysis of the effect of reducing ZNF658 expression by siRNA uncovered large changes in rRNA. We find that ZTREs are clustered within the 45S rRNA precursor. We also saw effects on expression of multiple ribosomal proteins. ZNF658 thus links zinc homeostasis with ribosome biogenesis, the most active transcriptional, and hence zinc-demanding, process in the cell. ZNF658 is thus a novel transcriptional regulator that plays a fundamental role in the orchestrated cellular response to zinc availability.
Publication Title
The zinc finger protein ZNF658 regulates the transcription of genes involved in zinc homeostasis and affects ribosome biogenesis through the zinc transcriptional regulatory element.
Sample Metadata Fields
Cell line
View Samples