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GSE4356
Mus musculus
27 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Deregulated expression of the Myc transcription factor is a frequent causal mutation in human cancer. Thousands of putative Myc target genes have been identified in in vitro studies, indicating that Myc exerts highly pleiotropic effects within cells and tissues. However, the complexity and diversity of Myc gene targets has confounded attempts at identifying which of these genes are the critical targets mediating Myc-driven tumorigenesis in vivo. Acute activation of Myc in a reversibly switchable transgenic model of Myc-mediated cell tumorigenesis induces rapid tumor onset whereas subsequent Myc de-activation triggers equally rapid tumor regression. Thus, sustained Myc activity is required for tumor maintenance. We have used this reversibly switchable kinetic tumor model in combination with high-density oligonucleotide microarrays to develop an unbiased strategy for identifying candidate Myc-regulated genes responsible for maintenance of Myc-dependent tumors. Consistent with known Myc functions, some Myc-regulated genes are involved in cell growth, cycle and proliferation. In addition, however, many Myc-regulated genes are specific to cells, indicating that a significant component of Myc action is cell-type specific. Finally, we identify a very restricted cadre of genes whose expression is inversely regulated upon Myc activation-induced tumor progression and de-activation-induced tumor regression. By definition, such genes are candidates for tumor maintenance functions. Combining reversibly switchable, transgenic models of tumor formation and regression with genomic profiling offers a novel strategy with which to deconvolute the complexities of oncogenic signaling pathways in vivo
Publication Title
Reversible kinetic analysis of Myc targets in vivo provides novel insights into Myc-mediated tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: The goal of the study was to integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signalling networks, relevant for rheumatoid arthritis (RA). Method:RNA-seq based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated RA patients, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of “connector” genes derived from pathway analysis was then tested for differential expression in the initial discovery cohort. Results: 11 qualifying genes were selected for pathway analysis and grouped into 2 evidence-based functional networks, containing 29 and 27 additional “connector” molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. 3 genes showed similar expression difference in both treated and non-treated RA patients and additional nine genes were differentially expressed in at least one patients' group compared to healthy controls. Conclusion: Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes in the pathogenesis of RA. Overall design: Illumina RNA-seq was performed on RNA from pereferial blood mononuclear cells taken from 12 healthy individuals, 5 untreated RA patients, and 7 treated RA patients
Publication Title
Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2000
Description
We provide data from several targeted deletions of transcriptional enhancer clusters within mouse F1 embryonic stem (ES) cells. We targeted these regions for deletion with CRISPR/Cas9 genome editing tools. We demonstrate through heterozygous enhancer cluster deletion and allele specific RNA-seq that enhancer clusters differ in their regulatory activity as the magnitude of the observed change in transcription upon enhancer cluster deletion varies greatly. Overall design: Strand specific RNA-seq after heterozygous or homozygous enhancer cluster deletion in mouse F1 ES cells (M. musculus129 x M. castaneus)
Publication Title
Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TCF7L2 is a master regulator of insulin production and processing.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here we harnessed the potential of expression arrays in 89 human pancreatic islet donors (different levels of blood glucose (HbA1c)) to identify genes regulated in this relevant tissue for type 2 diabetes (T2D).
Publication Title
TCF7L2 is a master regulator of insulin production and processing.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of HEK293 cells lines expressing V336Y mutant mitochondrial ribosomal protein. Overall design: mRNA profiles of wild-type and V336Y mutant HEK293 cell culture samples generated by deep sequencing.
Publication Title
Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- NextSeq 500
Description
Remodeling of chromatin accessibility is necessary for successful reprogramming of fibroblasts to neurons. However, it is still not fully known which transcription factors can induce a neuronal chromatin accessibility profile when overexpressed in fibroblasts. To identify such transcription factors, we here used ATAC-sequencing to generate differential chromatin accessibility profiles between human fibroblasts and iNeurons, an in vitro neuronal model system obtained by overexpression of Neurog2 in induced pluripotent stem cells (iPSCs). We found that the ONECUT transcription factor sequence motif was strongly associated with differential chromatin accessibility between iNeurons and fibroblasts. All three ONECUT transcription factors associated with this motif (ONECUT1, ONECUT2 and ONECUT3) induced neuronal morphology and expression of neuronal genes within two days of overexpression in fibroblasts. We observed widespread remodeling of chromatin accessibility; in particular, we found that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. There was substantial overlap with iNeurons, still, many regions that gained accessibility following ONECUT overexpression were not accessible in iNeurons. Our study highlights the potential of ONECUT transcription factors for direct neuronal reprogramming. Overall design: Each RNA-Seq experiment was performed in duplicate (library constructed from different wells of the same cell line in the same cell culture experiment). Bclxl controls were generated for the overexpression. experiments.
Publication Title
ONECUT transcription factors induce neuronal characteristics and remodel chromatin accessibility.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that core promoters are unidirectional and that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that about half of promoters are unidirectional and that these unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters. Overall design: Using 5''-GRO-seq and GRO-seq to determine mechanisms of divergent transcription initiation
Publication Title
Human promoters are intrinsically directional.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens, Rattus norvegicus
- 212 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray technology has had a profound impact on gene expression research. Some studies have questioned whether similar expression results are obtained when the same RNA samples are analyzed on different platforms.
Publication Title
The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.
Sample Metadata Fields
No sample metadata fields
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