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SRP038964
Homo sapiens
10 Downloadable Samples
IlluminaHiSeq2000
Description
ADARs are the primary factors underlying A-to-I editing in metazoans. We conducted the first global study of ADAR1-RNA interaction in human cells using CLIP-Seq. In contrast to the expected predominant binding of ADAR1 to Alu repeats, thousands of CLIP sites were located in non-Alu regions. This unexpectedly frequent non-Alu binding enabled discovery of transcriptome-wide functional and biophysical targets of ADAR1 in the regulation of mRNA processing including alternative 3'' UTR usage and alternative splicing. In addition, a global analysis of ADAR1 binding to non-Alu regions also revealed its primary interaction with microRNA (miRNA) transcripts in the nucleus, which subsequently affected expression levels of mature miRNAs. A complex global picture was revealed regarding the dependence of this function on the double-stranded RNA binding domains or deaminase activity. Our study unfolded a broad landscape of the diverse functional roles of ADAR1. Overall design: To identify ADAR binding dependent miRNA defferential expression profiles, U87MG cells were transfected with ADAR1 overexpression vector, RNA binding mutant (EAA and E912A), siRNA of ADAR1 or controls.
Publication Title
Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
ADARs are the primary factors underlying A-to-I editing in metazoans. We conducted the first global study of ADAR1-RNA interaction in human cells using CLIP-Seq. In contrast to the expected predominant binding of ADAR1 to Alu repeats, thousands of CLIP sites were located in non-Alu regions. This unexpectedly frequent non-Alu binding enabled discovery of transcriptome-wide functional and biophysical targets of ADAR1 in the regulation of mRNA processing including alternative 3'' UTR usage and alternative splicing. In addition, a global analysis of ADAR1 binding to non-Alu regions also revealed its primary interaction with microRNA (miRNA) transcripts in the nucleus, which subsequently affected expression levels of mature miRNAs. A complex global picture was revealed regarding the dependence of this function on the double-stranded RNA binding domains or deaminase activity. Our study unfolded a broad landscape of the diverse functional roles of ADAR1. Overall design: To charaterize ADAR1 binding profiles in U87 cells, we performed CLIP-seq using two different ADAR1 monoclonal antibodies.
Publication Title
Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 362 Downloadable Samples
- Illumina HiSeq 2000
Description
The genetics of messenger RNA expression has been extensively studied in humans and other organisms, but little is known about genetic factors contributing to microRNA (miRNA) expression. We examined natural variation of miRNA expression in adipose tissue in a population of 200 men who have been carefully characterized for metabolic syndrome phenotypes as part of the METSIM study. We genotyped the subjects using high-density SNP microarrays and quantified the mRNA abundance using genome-wide expression arrays and miRNA abundance using next generation sequencing. We reliably quantified 356 miRNA species that were expressed in human adipose tissue, a limited number of which made up most of the expressed miRNAs. We mapped the miRNA abundance as an expression quantitative trait and determined cis regulation of expression for 9 of the miRNAs and of the processing of one miRNA (miR-28). The degree of genetic variation of miRNA expression was substantially less than that of mRNAs. For the majority of the miRNAs, genetic regulation of expression was independent of the host mRNA transcript expression. We also showed that for 108 miRNAs, mapped reads displayed widespread variation from the canonical sequence. We found a total of 24 miRNAs to be significantly associated with metabolic syndrome traits. We suggest a regulatory role for miR-204-5p which was predicted to inhibit ACACB, a key fatty acid oxidation enzyme that has been shown to play a role in regulating body fat and insulin resistance in adipose tissue. Overall design: miRNA expression profiling of adipose tissue isolated from 200 humans
Publication Title
Genetic regulation of human adipose microRNA expression and its consequences for metabolic traits.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 628 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Oxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin.
Publication Title
Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 2000
Description
SNPs affecting disease risk often reside in non-coding genomic regions. Here we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPAR?, a nuclear receptor for antidiabetic drugs. Many such SNPs alter binding motifs for PPAR? or cooperating factors, and functionally regulate nearby genes whose expression is strain-selective and imbalanced in heterozygous F1 mice. Moreover, genetically-determined binding of PPAR? accounts for mouse strain-specific transcriptional effects of TZD drugs, providing proof-of- concept for personalized medicine related to nuclear receptor genomic occupancy. In human fat, motif-altering SNPs cause differential PPAR? binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors for dysmetabolic traits in genome- wide association studies. One PPAR? motif-altering SNP is associated with HDL levels and other metabolic syndrome parameters. Thus, natural genetic variation in PPAR? genomic occupancy determines individual disease risk and drug response. Overall design: Comparison of 5 RNA-seq experiments between 2 strains of mice differing in diet and fat depot. One of the experiments was evaluation of the response to a drug Rosiglitazone. Our RNA-seq data comprises primarily of 4 main experiments: The first experiment consists of samples taken from 2 strains of mice and their F1 progeny The samples are all taken from the same depot and when the mice were fed the same chow diet The second experiment has 2 parts, the first one involves samples taken from the 2 strains from the same eWAT depot when they were kept on a Low Fat Diet (LFD) This first part serves as a control for the second one in which the mice were treated with a drug, rosiglitazone in conjunction with a LFD The third experiment consists of samples taken from mice being fed on LFD. The samples are taken from the eWAT depot for both the strains. The fourth experiment consists of samples taken from mice being fed on LFD. The samples are taken from the iWAT depot for both the strains. We also have a solitary sample from a GRO-seq experiment which was done on eWAT in a B6 strain of mice being fed a LFD eWAT: epididymal White Adipose Tissue iWAT: inguinal White Adipose Tissue LFD-12w: mice were fed a control low fat diet (Research Diet D12450B) chow: mice were fed standard rodent chow Diet LFD w/rosiglitazone: Drug rosiglitazone (Cayman Chemicals) was incorporated into low fat diet D12450B by Research Diets at 36mg/kg of diet. Mice received control low fat diet for 10 weeks (age 6-16 weeks), and the rosiglitazone-containing diet versus control diet for the final 2 weeks (until sacrifice at 18 weeks) LFD control for rosi: mice were fed a control low fat diet (Research Diet D12450B)
Publication Title
Genetic Variation Determines PPARγ Function and Anti-diabetic Drug Response In Vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 185 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Identify genes in the epididymal adipose tissue whose expression is under genetic regulation in the hybrid mouse diversity panel. The hybrid mouse diversity panel is comprised of classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Bennett et al Genome Research 2010. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Publication Title
Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 770 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
We analyzed samples from 770 male human subjects who are part of the METSIM study. Ethics Committee of the Northern Savo Hospital District approved the study. All participants gave written informed consent. The population-based cross-sectional METSIM study included 10 197 men, aged from 45 to 73 years, who were randomly selected from the population register of the Kuopio town in eastern Finland (population 95000). Every participant had a 1-day outpatient visit to the Clinical Research Unit at the University of Kuopio, including an interview on the history of previous diseases and current drug treatment and an evaluation of glucose tolerance and cardiovascular risk factors. After 12 h of fasting, a 2 h oral 75 g glucose tolerance test was performed and the blood samples were drawn at 0, 30 and 120 min. Plasma glucose was measured by enzymatic hexokinase photometric assay (Konelab Systems reagents; Thermo Fischer Scientific, Vantaa, Finland). Insulin was determined by immunoassay (ADVIA Centaur Insulin IRI no. 02230141; Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA). Height and weight were measured to the nearest 0.5 cm and 0.1 kg, respectively. Waist circumference (at the midpoint between the lateral iliac crest and lowest rib) and hip circumference (at the level of the trochanter major) were measured to the nearest 0.5 cm. Body composition was determined by bioelectrical impedance (RJL Systems) in subjects in the supine position.
Publication Title
Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have shown that Sox10 plays a crucial role in the initiation and maintenance of giant congenital nevi and melanoma in a mouse model of melanoma.To dissect the molecular mechanisms and analyze the role of SOX10 in the maintenance of human melanoma, we have performed microarray study.
Publication Title
Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Follicular lymphoma (FL) is an indolent lymphoma associated with follicular center B cells, and typically contains the Bcl-2 chromosomal translocation t(14;18), which leads to overexpression of the anti-apoptotic intracellular protein Bcl-2. FLs are sensitive to chemotherapy; however, patient relapses occur and response duration becomes progressively shorter, with the majority of patients eventually dying from the disease. Enzastaurin (LY317615), an acyclic bisindolylmaleimide, was initially developed as an ATP-competitive selective inhibitor of PKC. We found, in agreement with recent reports, that enzastaurin inhibits cell proliferation and induces apoptosis. These results are consistent with decreased phosphorylation of the Akt pathway and its downstream targets. To provide new insights into the anti-tumor action of enzastaurin on non-Hodgkin lymphoma, we investigated its effects on gene expression profiles of the B cell lymphoma RL cell line by oligonucleotide microarray analysis. We identified a set of 41 differentially expressed genes, mainly involved in cellular adhesion, apoptosis, inflammation, and immune and defense responses. These observations provide new insights into the mechanisms involved in the induction of apoptosis by enzastaurin in B cell lymphoma cell lines, and identify possible pathways that may contribute to the induction of apoptosis.
Publication Title
Genomic profiling of enzastaurin-treated B cell lymphoma RL cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Metabolism in cancer serves to provide energy and key biomolecules that sustain cell growth, a process that is frequently accompanied by decreased mitochondrial use of glucose. Importantly, metabolic intermediates including mitochondrial metabolites are central substrates for post-translational modifications at the core of cellular signalling and epigenetics. However, the molecular means that coordinate the use of mitochondrial metabolites for anabolism and nuclear protein modification are poorly understood. Here, we unexpectedly found that genetic and pharmacological inactivation of Pyruvate Dehydrogenase A1 (PDHA1), a subunit of pyruvate dehydrogenase complex (PDC) that regulates mitochondrial metabolism16 inhibits prostate cancer development in different mouse and human xenograft tumour models. Intriguingly, we found that lipid biosynthesis was strongly affected in prostate tumours upon PDC inactivation. Mechanistically, we found that nuclear PDC controls the expression of Sterol regulatory element-binding transcription factor (SREBF) target genes by mediating histone acetylation whereas mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated effort to sustain anabolism. In line with the oncogenic function of PDC in prostate cancer, we find that PDHA1 and the PDC activator, Pyruvate dehydrogenase phospatase 1 (PDP1), are frequently amplified and overexpressed at both gene and protein level in these tumours. Taken together, our findings demonstrate that both mitochondrial and nuclear PDC sustains prostate tumourigenesis by controlling lipid biosynthesis thereby pointing at this complex as a novel target for cancer therapy.
Publication Title
Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.
Sample Metadata Fields
No sample metadata fields
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