Filters
Technology
Platform
SRP058860
Saccharomyces cerevisiae
31 Downloadable Samples
Illumina Genome Analyzer IIx, Illumina HiSeq 2500
Description
Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3’ single-stranded (3’-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses and double-stranded (ds)RNA mapping revealed that 3''-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anti-complementary transcripts protects cryptic intergenic lncRNAs from NMD. Our results indicate that aslncRNAs form dsRNA that are only translated and targeted to NMD if dissociated by Mtr4 and Dbp2. We propose that NMD buffers genome expression by discarding pervasive regulatory transcripts. Overall design: Strand-specific transcriptome analysis of biological replicates (1) of WT and xrn1-delta cells of the S288C, W303 and SK1 (n & 2n) genetic background of S. cerevisiae; (2) of WT, dcp2-7 and upf1-delta cells; (3) of WT, xrn1-delta and dcp2-7 cells upon treatment of total RNA with Terminator 5''-Phosphate-Dependent Exonuclease. This record also contains CAGE-Seq analysis in wild-type and decapping-deficient cells of the budding yeast S. cerevisiae.
Publication Title
Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double-Stranded RNA Structure.
Sample Metadata Fields
Subject
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes. Overall design: Strand-specific total RNA-Seq analysis in wild-type (WT) and dal80-delta (dal80) cells grown in glutamine- and/or proline-containing medium.
Publication Title
Transcription-dependent spreading of the Dal80 yeast GATA factor across the body of highly expressed genes.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
We have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (abbreviated as B) was substituted for that of A/J mice (ChrY<A>), cardiomyocytes from the resulting 'chromosome substitution' C57BL/6J-chrY<A> strain (abbreviated as B.Y) were smaller than that of their C57BL/6J counterparts. In reverse, when chrY<A> from A/J mice was substituted for that of chrY<B>, cardiomyocytes from the resulting A/J-chrY<C57> strain were larger than in their A/J counterparts. We further used these strains (B and the consomic B.Y) to test whether the origin of chrY could also be linked to differences in the profile of gene expression in their cardiac left ventricles in adult mice where either sham surgery (intact animals) or castration has been performed at 3-4 weeks of age..
Publication Title
Chromosome Y variants from different inbred mouse strains are linked to differences in the morphologic and molecular responses of cardiac cells to postpubertal testosterone.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The PAR-domain basic leucine zipper (PAR bZip) transcription factors DBP, TEF, and HLF accumulate in a highly circadian manner in several peripheral tissues, including liver and kidney. Mice devoid of all three of these proteins are born at expected Mendelian ratios, but are epilepsy-prone, age at an accelerated rate and die prematurely. In the hope of identifying PAR bZip target genes whose altered expression might contribute to the high morbidity and mortality of PAR bZip triple knockout mice, we compared the liver and kidney transcriptomes of these animals to those of wild-type or heterozygous mutant mice. These experiments revealed that PAR bZip proteins control the expression of many enzymes and regulators involved in detoxification and drug metabolism, such as cytochrome P450 enzymes, carboxylesterases, and constitutive androstane receptor (CAR). Indeed, PAR bZip triple knockout mice are hypersensitive to xenobiotic compounds, and the deficiency in detoxification may contribute to their early ageing.
Publication Title
The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogen receptors (ERs), which mediate the proliferative action of estrogens in breast cancer cells, are ligand-dependent transcription factors that regulate expression of their primary target genes through several mechanisms. In addition to direct binding to cognate DNA sequences, ERs can be recruited to DNA through other transcription factors (tethering), or affect gene transcription through modulation of signaling cascades by non-genomic mechanisms of action. To better characterize the mechanisms of gene regulation by estrogens, we have identified more than 700 putative primary and more than 1500 putative secondary target genes of estradiol in MCF7 cells through microarray analysis performed in the presence or absence of the translation inhibitor cycloheximide.
Publication Title
Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage.
Publication Title
CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We analysed the G-actin regulated transcriptome by gene expression analysis using previously characterised actin binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF) as well as unknown directly regulated genes.
Publication Title
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina HiSeq 2000
Description
Neuropathic pain is a complex chronic condition, characterized by a wide range of sensory, cognitive, and affective symptoms. Indeed, a large percentage of neuropathic pain patients are also afflicted with depression and anxiety disorders -- a pattern that is reliably replicated in animal models. Mounting evidence from clinical and preclinical studies indicates that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major determinant for depression. However, whether chronic pain and chronic stress affect similar mechanisms, and whether chronic pain can affect gene expression patterns known to be involved in depression, remains poorly understood. We employed the spared nerve injury model (SNI) of neuropathic pain in adult C57BL\6 mice and performed next-generation RNA-sequencing in order to monitor changes in gene expression in three brain regions known to be implicated in the pathophysiology of depression and in the modulation of pain: the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the periaqueductal grey (PAG). We observed mostly unique transcriptome profiles across the three brain regions but found common intracellular signal transduction pathways and biological functions were affected. A large amount of genes showing SNI-induced altered expression have been implicated in depression, anxiety, or chronic pain. In addition, we identified genes that are similarly regulated in a murine model of depression: chronic unpredictable stress. Our study provides the first unbiased characterization of neuropathic pain-induced long-term gene expression changes in three distinct brain regions, and presents evidence that neuropathic pain affects the expression of several genes that are also regulated by chronic stress. Overall design: RNA-seq samples were generated from 3 brain regions (nucleus accumbens, medial prefrontal cortex, and periaqueductal grey) of adult male mice, 2.5 months after sham or spared nerve injury to the sciatic nerve.
Publication Title
Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2000
Description
The paired-end next-generation sequencing of all small RNAs of less than 200 nucleotides in length from four different human cell lines (SKOV3ip1, MCF-7, BJ-Tielf, INOF) allowed us to determine the exact sequence(s) and variations of human box C/D snoRNAs (small nucleolar RNAs), revealing processing patterns of this class of molecules. Two distinct groups of box C/D snoRNAs were identified based on the position of their ends with respect to their characteristic boxes and the terminal base pairing potential. Short box C/D snoRNAs start sharply 4 or 5 nucleotides upstream of their box C and end 2 or 3 nucleotides downstream of their box D. In contrast, long box C/D snoRNAs start 5 or 6 nucleotides upstream of their box C and end 4 or 5 nucleotides downstream of their box D, increasing the likelihood of formation of a k-turn between their boxes C and D. Sequencing of SKOV3ip1 cells following the depletions of NOP58, a core box C/D snoRNA-binding protein and of RBFOX2, a splicing factor, shows that the short box C/D snoRNA forms are significantly more affected by the depletion of RBFOX2 while the long snoRNA forms, which display more canonical box C/D snoRNA features, are significantly more affected by the depletion of NOP58. Together the data suggest that box C/D snoRNAs are divided into at least two groups of RNA with distinct maturation and functional preferences. Overall design: Small RNAs (<200 nucleotides) were isolated from different human cell lines that were either untreated or depleted of NOP58 or RBFOX2 using specific siRNAs. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq.
Publication Title
Simultaneous sequencing of coding and noncoding RNA reveals a human transcriptome dominated by a small number of highly expressed noncoding genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
LPA is a natural bioactive lipid with growth factor-like functions due to activation of series of six G protein-coupled receptors (LPA1-6).
Publication Title
Identification of heparin-binding EGF-like growth factor (HB-EGF) as a biomarker for lysophosphatidic acid receptor type 1 (LPA1) activation in human breast and prostate cancers.
Sample Metadata Fields
Cell line
View Samples