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GSE68459
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We use mice containing a gene trap in the first intron of the Rest gene, which effectively eliminates transcription from all coding exons, to prematurely remove REST from neural progenitors. We find catastrophic DNA damage that occurs during S-phase of the cell cycle and concominant with activation of p53 pro-apoptotic sgnalling, with consequences including abnormal chromosome separation, apoptosis, and smaller brains.
Publication Title
The REST remodeling complex protects genomic integrity during embryonic neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
We use mice containing a gene trap in the first intron of the Rest gene, which effectively eliminates transcription from all coding exons, to prematurely remove REST from neural progenitors. We find catastrophic DNA damage that occurs during S-phase of the cell cycle, with consequences including abnormal chromosome separation, apoptosis, and smaller brains. Further support for persistent effects is the latent appearance of proneural glioblastomas in adult mice also lacking the tumor suppressor, p53. A Rest deficient mouse line generated previously, using a conventional gene targeting approach, does not exhibit these phenotypes, likely due to a remaining C terminal peptide that still binds chromatin and recruits REST chromatin modifiers.Our results indicate that REST-mediated chromatin remodeling is required for proper S-phase dynamics, prior to its well-established role in relieving repression of neuronal genes at terminal differentiation.
Publication Title
The REST remodeling complex protects genomic integrity during embryonic neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Transcription cofactor Rcor1 has been linked biochemically both to neurogenesis and hematopoiesis. Here we studied the function of Rcor1 in vivo and showed it is essential to erythropoeisis during embryonic development. Rcor1 mutant proerythroblasts, unlike normal cells, can form myeloid colonies in vitro. To investigate the underlying molecular mechanisms for block of erythropoiesis and increased myeloid potential, we used RNA-seq to reveal the differentially expressed genes from erythroid progenitors due to depletion of Rcor1. Overall design: RNA were extracted from FACS sorted CD71+,TER119- erythroid progenitors from control (Rcor1+/+ and Rcor1+/-) or Mutant (Rcor1-/- ) E13.5 fetal liver. Each library was made by pooling RNA from several fetal livers. Two biological replicates were made for either control or mutant condition.
Publication Title
Corepressor Rcor1 is essential for murine erythropoiesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Hepatitis C virus (HCV) is widely used to investigate host-virus interactions and cellular responses to infection have been extensively studied in vitro. In human liver, interferon (IFN) stimulated gene expression can mask direct transcriptional responses to virus infection. To better characterize the direct effects of HCV infection in vivo, we analyze the transcriptomes of HCV-infected patients lacking an activated endogenous IFN system. We show that the expression changes observed in these patients predominantly reflect immune cell infiltrates rather than changes in cell-intrinsic metabolic pathways. We also investigate the transcriptomes of patients with endogenous IFN activation, which paradoxically cannot eradicate viral infection. We find that most IFN-stimulated genes (ISGs) are induced by both the endogenous IFN system and by recombinant IFN therapy, but with significantly higher induction levels in the latter. We conclude that the innate host immune response in chronic hepatitis C is too weak to clear the virus. Overall design: In this study, we aimed to disentangle the direct and indirect effects of HCV infection on cellular transcriptional profiles, by performing a detailed characterization of the gene expression changes associated with HCV infection, endogenous IFN system activation and pegIFNa treatment in the human liver. With this objective, we generated and analyzed high-throughput transcriptome sequencing profiles from liver biopsies derived from different categories of HCV-infected and non-infected patients, prior to and during treatment. First, to unveil HCV-induced cell-autonomous effects and to separate them from IFN-induced changes in the transcriptome, we selected liver biopsies from patients with chronic hepatitis C (CHC) without hepatic ISG induction, and compared them with un-infected control biopsies. Second, we examined the transcriptomic changes associated with the endogenous activation of the IFN system. Finally, we analyzed the gene expression changes resulting from pegIFNa/ribavirin treatment, by comparing transcriptome data from liver biopsies obtained before treatment and at different time points during the first week of therapy.
Publication Title
Transcriptional response to hepatitis C virus infection and interferon-alpha treatment in the human liver.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Despite decades of interest, the mechanisms that control Hox gene expression are not yet fully understood. It was recently proposed that Hotair, a lncRNA transcribed from the HoxC cluster, regulates HoxD gene expression via Polycomb targeting and thus is important for correct skeletal development. However, genetic manipulations of the locus led to conflicting results regarding the roles of Hotair. Here, we analyze the molecular and phenotypic consequences of deleting the Hotair locus in vivo. In contradiction with previous findings, we show that deleting Hotair has no detectable effect on HoxD gene expression in vivo. We could not observe any morphological alteration in mice lacking the Hotair locus. However, we find a significant impact of deleting Hotair on the expression of neighboring genes Hoxc11 and Hoxc12. Our results do not support an RNA-dependent role for Hotair in vivo, but argue in favor of a DNA-dependent effect of Hotair deletion on the transcriptional landscape in cis. Overall design: We micro-dissected wild type and Del(Hotair)-/- E12.5 embryos into 6 segments: forelimbs (FL), hindlimbs (HL), genital tubercle (GT), trunk section corresponding to the lumbar/sacral region (T1); trunk section corresponding to the sacral/caudal region (T2) and trunk section corresponding to the caudal region (T3). We generated strand-specific RNA-seq data for each segment, in two biological replicates and we performed differential expression analyses for each tissue. Furthermore, we analyzed the impact of deleting the Hotair locus on the local transcriptional landscape, in the HoxC cluster.
Publication Title
Hotair Is Dispensible for Mouse Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
In this work we have analyzed the transcriptomic profiles of E9 mouse embryos. We show that Hoxd1 and Haglr transcripts are absent after targeted deletion of the CpG: 114 island. Overall design: RNA-seq analysis of trunk from the anterior limit of the forelimb bud to the tailbud, aiming to exclude all extra-embryonic, head, cervical and heart tissues. Individuals 443 (wt) and 445 (Del(CpG114) homozygous), were siblings from the same dam, while biological replicates 456 (wt) and 455 (Del(CpG114) homozygous) were siblings from another dam.
Publication Title
Control of growth and gut maturation by <i>HoxD</i> genes and the associated lncRNA <i>Haglr</i>.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
To determine the physiological targets of the NELF complex, and provide insight into the mechanism of NELF activity in vivo.
Publication Title
NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have used an agnostic approach to identify drug combinations by using combination high throughput screening (cHTS) technology and make the surprising discovery that adenosine A2A and beta-2 adrenergic receptor agonists are highly synergistic, selective and novel agents that enhance glucocorticoid activity in B-cell malignancies.
Publication Title
Adenosine A2A and beta-2 adrenergic receptor agonists: novel selective and synergistic multiple myeloma targets discovered through systematic combination screening.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Regulation of gene expression is integral to the development and survival of all organisms. Transcription begins with the assembly of a pre-initiation complex at the gene promoter, followed by initiation of RNA synthesis and the transition to productive elongation. In many cases, recruitment of RNA polymerase II (Pol II) to a promoter is necessary and sufficient for activation of gene. However, there are a few notable exceptions to this paradigm, including heat shock genes and several proto-oncogenes, whose expression is attenuated by regulated stalling of polymerase elongation within the promoter-proximal region. To determine the importance of polymerase stalling for transcription regulation, we performed a genome-wide search for Drosophila genes with promoter-proximally stalled Pol II. Our data reveal that stalling is widespread, occurring at hundreds of genes that respond to stimuli and developmental signals, indicating a role for regulation of polymerase elongation in the transcriptional responses to dynamic environmental and developmental cues.
Publication Title
RNA polymerase is poised for activation across the genome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
An assessment of a role of Ebf1 in committed B lineage cells.
Publication Title
Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells.
Sample Metadata Fields
Specimen part
View Samples