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SRP013468
Saccharomyces cerevisiae
6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Anti-sense non-coding transcripts, genes-within-genes, and convergent gene pairs are prevalent among eukaryotes. The existence of such transcription units raises the question of what happens when RNA polymerase II (RNAPII) molecules collide head-to-head. Here we use a combination of biochemical and genetic approaches in yeast to show that polymerases transcribing opposite DNA strands cannot bypass each other. RNAPII stops, but does not dissociate upon head-to-head collision in vitro, suggesting that opposing polymerases represent insurmountable obstacles for each other. Head-to-head collision in vivo results in RNAPII stopping as well, and removal of collided RNAPII from the DNA template can be achieved via ubiquitylation-directed proteolysis. Indeed, in cells lacking efficient RNAPII poly-ubiquitylation, the half-life of collided polymerases increases, so that these can be detected between convergent genes by ChIP-Seq. These results provide new insight into fundamental mechanisms of gene traffic control, and point to an unexplored effect of anti-sense transcription on gene regulation via polymerase collision. Overall design: Total RNA was extracted from WT or Elongin C deletion mutant (elc1?) cells and strand-specific RNA-Seq was performed. Three biological replicates were performed for WT and elc1?.
Publication Title
RNA polymerase II collision interrupts convergent transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Pseudomonas aeruginosa
- 24 Downloadable Samples
Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
To provide a more detailed survey of adaptive changes in the physiology of P. aeruginosa (PA) during long-term infection of the cystic fibrosis (CF) lung, we performed a comparative proteome and transcriptome analysis of a set of isogenic sequential non-mutator and mutator isolates from three selected CF patients. Recently, we showed that during CF lung persistence PA mutators converge to a virulence-attenuated phenotype. In this study, we demonstrate that besides virulence-associated traits (VATs) the adaptation process of PA predominantly comprises metabolic pathways. In end-stage mutator strains, transcripts of genes encoding VATs, chemotaxis, degradation of aromatic compounds and several two-component regulatory systems were decreased. In contrast, several transcripts of genes or proteins involved in metabolism of fatty acids, nucleotides, amino acids and the generation of energy were increased. Of particular interest is the increased expression level of genes involved in (i) the anaerobic arginine-deiminase pathway, (ii) the anaerobic respiration such as nitrate-uptake protein OprF, redox-active azurin and cytchrome c551 peroxidase, (iii) the micro-aerobic respiration such as high oxygen-affinity cytochrome oxidase cbb3 (iv) the tricarboxylic acid cycle (TCA), glyoxylate shunt and anaplerotic carboxylation reactions to oxaloacetate. Strikingly, an increased transcription of the anaerobic regulator gene anr correlates with the up-regulation of ANR-dependent genes. In conclusion, these changes in transcriptome and proteome indicate an adaptive shift towards constitutive expression of genes of metabolic pathways obviously required for growth under micro-aerobic and nutritional conditions of suppurative CF lung tissue. Finally, these results provide us with new targets for antimicrobial agents and biomarkers reflecting adaptation of PA towards progressive CF lung disease.
Publication Title
Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 169 Downloadable Samples
- IonTorrentProton
Description
We explored mechanisms of carcinogenicity of acrylamide in the rat thyroid. We compared the transcriptome profiles of target(thyroid) vs non-target(liver) tissues.
Publication Title
Transcriptional profiling of male F344 rats suggests the involvement of calcium signaling in the mode of action of acrylamide-induced thyroid cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine.
Publication Title
Epigenetic silencing of novel tumor suppressors in malignant melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We sequenced mRNA from 12 samples extracted from mouse amygdala tissue to generate the first amygdala-specific murine transcriptome for germ-free mice (GF), conventionally raised controls (CON) and germ-free mice that have been colonized with normal microbiota from postnatal day 21 (exGF). Overall design: Equal amounts of RNA from two to three animals were pooled to yield 4 samples per group (CON, GF, and exGF). Pairwise comparisons for CONvsGF, CONvsexGF, GFvsexGF were performed using DESeq2.
Publication Title
Microbes & neurodevelopment--Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 29 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
During seed maturation, the embryo accumulates nutrition storage compounds such as oil and reservve proteins, and acquires dormancy and desiccation tolerance. Arabidopsis transcription factors LEC1, LEC2, FUS3 and ABI3 are known as the master regulators of seed maturation because all these events during the seed maturation are severely affected by the respective mutants. In addition, the lec1, lec2 and fus3 mutants exhibit some heterochronic characteristics, as exemplified by the development of true leaf-like cotyledons during embryogenesis. To characterize these mutants at the whole genome expression level, microarray experiments were performed.
Publication Title
Cell-by-cell developmental transition from embryo to post-germination phase revealed by heterochronic gene expression and ER-body formation in Arabidopsis leafy cotyledon mutants.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
The undifferentiated spermatogonial population of mouse testis is known to be functionally heterogeneous and contain both stem cells and committed progenitor cells. However, gene expression patterns marking these distinct cell fractions are poorly defined. We found that a subset of undifferentiated spermatogonia were marked by expression of a PDX1-GFP transgene but properties of these cells were unclear. Undifferentiated cells were therefore isolated from adult testes and separated according to expression of PDX1-GFP+ for gene expression analysis by RNA-seq. Our goal was to identify differentially expressed genes from PDX1-GFP+ vs PDX1-GFP- with that of known markers of stem and committed progenitor cells. Overall design: 4 independent sets of PDX1-GFP-positive and PDX1-GFP-negative undifferentiated spermatogonia were isolated by flow sorting from adult mouse testes.
Publication Title
Identification of dynamic undifferentiated cell states within the male germline.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
Sustained spermatogenesis in adult males and recovery of fertility following germ cell depletion are dependent on undifferentiated spermatogonia with self-renewal potential. We have previously demonstrated a critical cell-autonomous role for Gilz in spermatogonial stem cell maintainance and spermatogenesis. To identify genes regulated by Gilz in the male germline, we have isolated undifferentiated spermatogonial cells from tamoxifen treated Gilzflox/flox (Control) and Gilzflox/flox UBC-CreER (TAM-KO) mice that will allow identification of genes mis-expressed upon loss of GILZ. Overall design: 4 independent sets of Gilzflox/flox (Control) and Gilzflox/flox UBC-CreER (TAM-KO) undifferentiated spermatogonia were isolated by flow sorting from adult mouse testes 7 days after treatment with tamoxifen.
Publication Title
GILZ-dependent modulation of mTORC1 regulates spermatogonial maintenance.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Effects of maternal obesity on Wharton's Jelly mesenchymal stromal cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Sickle cell disease (SCD) results from a point mutation in the ß-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)–like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell–derived erythroid progenitors. We investigated the ability of dimethyl fumarate (DMF), a small-molecule Nrf2 agonist, to activate ?-globin transcription and enhance HbF in tissue culture, murine and primate models. DMF recruited Nrf2 to the ?-globin promoters and the locus control region of the ß-globin locus in erythroleukemia cells, elevated HbF in SCD donor–derived erythroid progenitors, and reduced hypoxia-induced sickling. Chronic DMF administration in SCD mice induced HbF and increased Nrf2-dependent genes to detoxify heme and limit inflammation. This improved hematological parameters, reduced plasma-free Hb, and attenuated inflammatory markers. Chronic DMF administration to nonanemic primates increased ?-globin mRNA in BM and HbF protein in red cells. DMF represents a potential therapy for SCD to induce HbF and augment vasoprotection and heme detoxification Overall design: RNA-Seq of 30 samples
Publication Title
Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and corrects anemia in sickle cell disease.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples