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E-MEXP-580
Saccharomyces cerevisiae
18 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
Nitric oxide and NO-derived species (RNS) are defense molecules with broad antimicrobial activity. Micro-organisms have developed strategies to sense RNS and counteract their damaging effects. We used Saccharomyces cerevisiae, harbouring a deletion of YHB1 that encodes the main NO scavenger enzyme, to study consequences of RNS exposure on whole genome transcriptional response. The expression of >700 genes was altered on RNS treatment. No major role for ROS-scavenging enzymes was found, and the respiratory chain, the main site of ROS production, had only minor involvement in the RNS-induced stress. The changes were generally transient and also found after treatment with the respiratory inhibitor myxothiazol. 117 genes however showed a persistent response which was not observed after myxothiazol treatment. Of these, genes of the glutathione and DNA repair systems, iron homeostasis and transport were found up-regulated. Severe repression of genes of respiratory chain enzymes was observed. Many of these genes are known to be regulated by the transcription factor Hap1p suggesting that RNS might interfere with Hap1p activity. We showed also that Msn2/4p and Yap1p, key regulators of the response to, respectively, general stress and oxidative stress, played a role in mediating the RNS-induced response.
Publication Title
Transcriptional response to nitrosative stress in Saccharomyces cerevisiae.
Sample Metadata Fields
Compound, Time
View Samples- Saccharomyces cerevisiae
- 29 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The mitochondrial respiratory chain is composed of lipoprotein complexes imbedded in the inner mitochondrial membrane. This chain of enzymes transfers electrons from NADH and FADH2, provided from divers metabolic pathways, to oxygen. It couples the transfer of electrons to the translocation of protons across the membrane. Several clinical syndromes have been associated with respiratory dysfunction caused by mitochondrial or nuclear mutations. A number of mutations in the mitochondrial genes encoding for cytochrome b (CYTB) and cytochrome oxidase (COX 1, 2 and 3) have been linked with diseases. We are using yeast mutants to characterize the deleterious effect of mutations reported in patients on the assembly and catalytic properties of the affected enzymes, and to study the impact of mutations in nuclear genes, such as OXA1, encoding for factors required for the assembly of the respiratory complexes. In this work, we monitored the effects of the mutations causing respiratory defect on the whole genome expression. We compared the change in gene expression in rho0 cells (with a complete deletion of the mitochondrial genome, and by consequence without respiratory chain), in cells with either a single defective enzyme or several, and in cells after prolonged treatment with the bc1 inhibitors myxothiazol or antimycin. The impact of the mutations on the respiratory function ranged from mild to severe. The expression of approx. 350 genes was changed in at least one mutant. Cluster analysis was performed using the Cluster program (Eisen, 1998, PNAS 95:14863). Four groups of genes were studied in more details: Group A, the most repressed genes; Group B, the most over-expressed genes; Group C, genes more repressed in rho0 and Doxa1 cells; and Group D, genes more over-expressed in Doxa1.
Publication Title
Multiple defects in the respiratory chain lead to the repression of genes encoding components of the respiratory chain and TCA cycle enzymes.
Sample Metadata Fields
Compound
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic mice were generated that expressed the inhibitor of apoptosis and mitotic regulator survivin in pancreatic islet beta cells. Control non-transgenic or transgenic islets were then used in a model of islet transplantation in diabetic recipient mice and tested for their ability to correct hyperglycemia and allow long-term engraftment of tranplanted islets in vivo. Control or transgenic islets were analyzed by chip microarray for potential transcriptional changes associated with transgenic expression of survivin, in vivo.
Publication Title
Genome-wide analysis of Polycomb targets in Drosophila melanogaster.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters (DTPs) that is dynamically maintained within a wide variety of tumor cell populations. Here, we explored a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs revealed miR-371-3p as a potent suppressor of drug tolerance. PRDX6 (peroxiredoxin 6) was identified as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKC activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of PRDX6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance.
Publication Title
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters (DTPs) that is dynamically maintained within a wide variety of tumor cell populations. Here, we explored a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs revealed miR-371-3p as a potent suppressor of drug tolerance. PRDX6 (peroxiredoxin 6) was identified as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKC activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of PRDX6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance.
Publication Title
Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Effect of absence of interaction with MHC class II on memory CD4 T cells
Publication Title
Noncognate interaction with MHC class II molecules is essential for maintenance of T cell metabolism to establish optimal memory CD4 T cell function.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
In order to investigate the impact of MMP-14 (MT1-MMP) and three-dimensional (3D) culture conditions on the transcriptomes of a human breast adenocarcinoma cell line, we performed a microarray analysis from RNAs isolated from MCF-7 cells expressing either an empty vector (CTRL) or human MMP-14 cDNA (MT1) in monolayer (2D) and 3D collagen (3D Col) growth conditions.
Publication Title
A membrane-type-1 matrix metalloproteinase (MT1-MMP)-discoidin domain receptor 1 axis regulates collagen-induced apoptosis in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The LXCXE peptide motif facilitates interaction between the RB tumor suppressor and a large number of cellular proteins that are expected to impinge on diverse biological processes. In vitro and in vivo analyses demonstrated that LXCXE-binding function is dispensable for RB promoter association and control of basal gene expression. Dependence on this function of RB is unmasked after DNA damage, wherein LXCXE-binding is essential for exerting control over E2F3 and suppressing cell cycle progression in the presence of genotoxic stress. Gene expression profiling revealed that the transcriptional program coordinated by this specific aspect of RB is associated with progression of human hepatocellular carcinoma and poor disease outcome. Consistent with these findings, biological challenge revealed a requirement for LXCXE-binding in suppression of genotoxin-initiated hepatocellular carcinoma in vivo. Together, these studies establish an essential role of the LXCXE-binding motif for RB-mediated transcriptional control, response to genotoxic insult, and tumor suppression.
Publication Title
RB restricts DNA damage-initiated tumorigenesis through an LXCXE-dependent mechanism of transcriptional control.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated genomic analysis of colorectal cancer progression reveals activation of EGFR through demethylation of the EREG promoter.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples