Filters
Technology
Platform
GSE96997
Saccharomyces cerevisiae
142 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Transcript dynamics in mitotic exit mutants in the S. cerevisiae BF264-15D strain background. We examined the extent to which periodic cell-cycle transcription persisted in cells arrested in anaphase with intermediate level of B-cyclins.
Publication Title
Reconciling conflicting models for global control of cell-cycle transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
During HIV-1 infection, there is a massive perturbation of host gene expression, but as yet, genome-wide studies have not identified host genes affecting HIV-1 replication in lymphatic tissue, the primary site of virus-host interactions. In this study, we isolated RNA from the inguinal lymph nodes of 22 HIV-1-infected individuals and utilized a microarray approach to identify host genes critically important for viral replication in lymphatic tissue by examining gene expression associated with viral load. Strikingly, ~95% of the transcripts (558) in this data set (592 transcripts total) were negatively associated with HIV-1 replication. Genes in this subset (1) inhibit cellular activation/proliferation (ex.: TCFL5, SOCS5 and SCOS7, KLF10), (2) promote heterochromatin formation (ex.: HIC2, CREBZF, ZNF148/ZBP-89), (3) increase collagen synthesis (ex.: PLOD2, POSTN, CRTAP), and (4) reduce cellular transcription and translation. Potential anti-HIV-1 restriction factors were also identified (ex.: NR3C1, HNRNPU, PACT). Only ~5% of the transcripts (34) were positively associated with HIV-1 replication. Paradoxically, nearly all these genes function in innate and adaptive immunity, particularly highlighting a heightened interferon system. The predominance of negative correlations as well as the disconnect between host defenses and viral load point to the importance of genes that regulate target cell activation and genes that code for potentially new restriction factors as determinants of viral load rather than conventional host defenses.
Publication Title
Host genes associated with HIV-1 replication in lymphatic tissue.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation, whereas its role in leukemia propagation and maintenance remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines. Findings: Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-DOWN set was significantly enriched for genes included in the cell activation, immune response, apoptosis, signal transduction and development and differentiation categories, whereas in the E/R KD-UP set only the PI3K/AKT/mTOR signaling and hematopoietic stem cells categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories stem cell properties, B-cell differentiation, immune response, cell adhesion and DNA damage with RT-qPCR. Conclusion: The results of our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with regular B-cell development by repressing key functions that are necessary under physiological circumstances. E/R may thus constitute also the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.
Publication Title
The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
DU145 prostate cancer cells were treated with 50 ng/ml FGF19 and 50 ug/ml heparin, or 10 ng/ml TNFalpha, or both
Publication Title
The receptor tyrosine kinase FGFR4 negatively regulates NF-kappaB signaling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Untreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
Publication Title
Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race, Subject
View Samples- Pseudomonas aeruginosa pao1, Pseudomonas aeruginosa
- 16 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2000
Description
The ubiquitous efflux transporter ATP-binding cassette sub-family C member 5 (ABCC5) is present at high levels in the blood-brain barrier, neurons and glia, but its in vivo substrates and function are not known. Untargeted metabolomic screens revealed that Abcc5-/- mice accumulate endogenous glutamate conjugates and analogs in several tissues, but brain in particular. The abundant neurotransmitter N-acetylaspartylglutamate (NAAG), for example, was over 2-fold higher in Abcc5-/- brain. In line with ABCC5-mediated transport, the metabolites that accumulated in Abcc5-/- tissues were depleted in cultured cells that overexpressed human ABCC5. Using membrane vesicles, we show that ABCC5 not only transports the metabolites detected in our screen, but also a wide range of peptides containing a C-terminal glutamate. Glutamate conjugates are of physiological relevance because they can affect the function of glutamate, the principal excitatory neurotransmitter in the brain. We found that ABCC5 also transports exogenous glutamate analogs, like the classic excitotoxic neurotoxins kainic acid, domoic acid and N-methyl-D-aspartate (NMDA) and the therapeutic glutamate analog ZJ43. Taken together, we have identified ABCC5 as a general glutamate conjugate and analog transporter that affects the disposition of endogenous metabolites, toxins and drugs. Overall design: A set of 5 wildtype brains was compared to a set of 5 Abcc5-knockout mouse brains
Publication Title
ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa pao1, Pseudomonas aeruginosa
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The opportunistic human pathogen Pseudomonas aeruginosa can utilize several carbon and nitrogen compounds as energy sources, which allows the bacterium to grow on a variety of different environments. Nevertheless, the uptake and utilization of these compounds is organized in a hierarchical manner, which is guaranteed by a mechanism named catabolite repression. In P. aeruginosa catabolite repression is a post-transcriptional process with the translational repressor protein, Crc, as the main component. Crc recognizes CA-motifs (acronym for catabolite activity) present in the vicinity of the ribosome binfing site of corresponding target mRNAs and therefore compete with ribosome binding. Certain conditions, which are mainly related to changes in the carbon to nitrogen ratio, induce the two component system CbrAB, which activates the transcription of the sRNA CrcZ. The sRNA sequesters Crc and allows the translation of the target mRNAs. The main focus of this study was to identify novel direct targets of the CbrAB/Crc system with the use of a transcriptome analysis in combination with the search for CA-motifs. We were able to identify five novel targets (estA, acsA, dctP, bkdR and aroP2), which were involved in the uptake and utilization of less preferred carbon sources and amino acids. Direct interaction of Crc with these genes and the resulting regulation by CbrB and CrcZ were verified using mutational analysis and in vitro and in vivo experiments. Moreover, these targets were discussed in the light of growth and biofilm development in synthetic CF sputum medium which emphasised the importance of the CbrAB/Crc system as a regulator of chronic infection.
Publication Title
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa pao1, Pseudomonas aeruginosa
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The opportunistic human pathogen Pseudomonas aeruginosa can utilize several carbon and nitrogen compounds as energy sources, which allows the bacterium to grow on a variety of different environments. Nevertheless, the uptake and utilization of these compounds is organized in a hierarchical manner, which is guaranteed by a mechanism named catabolite repression. In P. aeruginosa catabolite repression is a post-transcriptional process with the translational repressor protein, Crc, as the main component. Crc recognizes CA-motifs (acronym for catabolite activity) present in the vicinity of the ribosome binfing site of corresponding target mRNAs and therefore compete with ribosome binding. Certain conditions, which are mainly related to changes in the carbon to nitrogen ratio, induce the two component system CbrAB, which activates the transcription of the sRNA CrcZ. The sRNA sequesters Crc and allows the translation of the target mRNAs. The main focus of this study was to identify novel direct targets of the CbrAB/Crc system with the use of a transcriptome analysis in combination with the search for CA-motifs. We were able to identify five novel targets (estA, acsA, dctP, bkdR and aroP2), which were involved in the uptake and utilization of less preferred carbon sources and amino acids. Direct interaction of Crc with these genes and the resulting regulation by CbrB and CrcZ were verified using mutational analysis and in vitro and in vivo experiments. Moreover, these targets were discussed in the light of growth and biofilm development in synthetic CF sputum medium which emphasised the importance of the CbrAB/Crc system as a regulator of chronic infection.
Publication Title
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studies in vitro and in mice indicate a role for Coenzyme Q10 (CoQ10) in gene expression. To determine this function in relationship to physiological readouts, a 2-week supplementation study with the reduced form of CoQ10 (ubiquinol, Q10H2, 150 mg/d) was performed in 53 healthy males. Mean CoQ10 plasma levels increased 4.8-fold after supplementation. Transcriptomic and bioinformatic approaches identified a gene-gene interaction network in CD14-positive monocytes, which functions in inflammation, cell differentiation and PPAR-signaling. These Q10H2-induced gene expression signatures were also described previously in liver tissues of SAMP1 mice. Biochemical as well as NMR-based analyses showed a reduction of LDL cholesterol plasma levels after Q10H2 supplementation. This effect was especially pronounced in atherogenic small dense LDL particles (19-21 nm, 1.045 g/l). In agreement with gene expression signatures, Q10H2 reduces the number of erythrocytes but increases the concentration of reticulocytes. In conclusion, Q10H2 induces characteristic gene expression patterns, which are translated into reduced LDL cholesterol levels and erythropoiesis in humans.
Publication Title
Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples