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GSE106073
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Converting epithelial into mesenchymal cells through epithelial-mesenchymal transition (EMT) requires massive changes in gene expression. How this is brought about is currently not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anti-correlated in transcriptomes of colorectal tumors and cell lines. In two cellular EMT models, ectopically expressed Snail1 downregulates FOXA factors and directly represses FOXA1. To elucidate how FOXA factors contribute to the control of epithelial gene expression, we determined by ChIP-seq data analysis FOXA chromosomal distribution in relation to chromatin structural features characterizing distinct states of transcriptional activity. This revealed a preferential localization of FOXA1 and FOXA2 to transcriptional enhancers at signature genes that distinguish epithelial from mesenchymal colon tumors. To validate the significance of this association, we investigated the impact of FOXA factors on structure and function of transcriptional enhancers at the epithelial genes CDH1, CDX2 and EPHB3. Expression of dominant negative FOXA2 led to chromatin condensation at these enhancer elements. Site- directed mutagenesis of FOXA binding sites in reporter gene constructs and by genome- editing in situ impaired enhancer activity and completely abolished the active chromatin state of the EPHB3 enhancer. Conversely, expression of FOXA factors in cells with inactive CDX2 and EPHB3 enhancers led to chromatin opening and de novo deposition of the H3K4me1 and H3K27ac marks. These findings establish the pioneer function of FOXA factors at enhancer regions of epithelial genes and demonstrate their essential role in maintaining enhancer structure and function. Thus, by repressing FOXA family members, Snail1 targets transcription factors at strategically important positions in gene-regulatory hierarchies which may facilitate transcriptional reprogramming during EMT.
Publication Title
SNAIL1-mediated downregulation of FOXA proteins facilitates the inactivation of transcriptional enhancer elements at key epithelial genes in colorectal cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide association studies in multiple sclerosis (MS) identified a polymorphism (rs6897932) located in the coding region of the alpha chain of the cytokine receptor interleukin 7 receptor (IL7R) as a component that increases susceptibility to develop the disease. This single nucleotide polymorphism (SNP) affects the splicing of the primary transcript leading to genotype-defined transcript ratios encoding either a full length membrane spanning form or a soluble receptor chain. Genotyping at the IL7R locus reveals that the region can be described by four haplotypes. Interestingly, only one out of three haplotypes harbouring the associated SNP is positively associated with MS whereas the other two do not show association. The minor allele containing haplotype shows a reduced susceptibility to develop MS. We hypothesized that additional functional or phenotypic differences exist between individuals homozygous for haplotypes shown to have either positive, negative, or neutral effect, on susceptibility to develop MS. Gene expression profiles of CD4+ T cells from MS individuals before and after stimulation with IL7 were recorded. Haplotype-specific gene signatures were found indicating small alterations in IL7/IL7R signal processing/sensitivity through JAK/STAT and p38/MAPK14. We can not exclude that the obtained signatures result from differences within the CD4+ T cell compartment that, in fact, should be seen as a consequence of systemic haplotype-specific processing of homeostatic and proliferation signals transmitted through IL7/IL7R.
Publication Title
IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaGenomeAnalyzerIIx
Description
Using doxycycline-inducible IFN-kappa expression in CIN612-9E cells, which maintain extrachromosomally replicating HPV31 genomes, we demonstrate that IFN-kappa inhibits the growth of these cells and reduces viral transcription and replication. Interestingly, the initiation of viral early transcription was already inhibited 4-6h after IFN-kappa expression. This was also observed with recombinant IFN-beta suggesting a common mechanism of IFNs. RNA-seq analysis identified 1367 IFN-kappa regulated genes of which 221 were modulated >2-fold. The majority of those (71%) matched known ISGs confirming that IFN-kappa acts as a bona fide type I IFN in hr-HPV-positive keratinocytes. RNAi and co-transfection experiments indicate that the inhibition of viral transcription is mainly due to the induction of Sp100 proteins by IFN-kappa. Overall design: CIN612-9E/pInd-IFN-kappa were induced for 4h with 1µg/ml doxycyclin or not. Three biological replicates were analyzed.
Publication Title
Interferon Kappa Inhibits Human Papillomavirus 31 Transcription by Inducing Sp100 Proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 29 Downloadable Samples
- Illumina HiScanSQ, Illumina HiSeq 2500
Description
Naive spleens as well as naive and LPS-treated dendritic cells from wildtype and GPR34-/- mice were sequenced to integrate expression profiles with protein interaction networks and find functional modules that are affected by GPR34 Overall design: Expression profiles of dendritic cells and whole spleens were generated using Illumina HiSeq 2500/ Illumina HiScan
Publication Title
Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence.
Sample Metadata Fields
No sample metadata fields
View Samples- Ovis aries
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
Fracture healing is a highly complex regenerative process. The sheep is an important large-animal model for studying delayed fracture healing. Here we used next-generation sequencing (Illimuna GA IIx) for gene expression analysis (RNAseq) in two conditional groups - standard and delayed healing. In both groups sequential biopsies 7, 11, 14 and 21 days after surgery were collected from callus tissue and annalized. For all timepoints and conditions the samples were pooled (n=6), except for day 21 standard (n=5).
Publication Title
Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions and its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalyzing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. Using a combination of literature information, transcription factor prediction models and genome-wide expression arrays, we inferred the regulatory network of IRG1 in mouse and human macrophages.
Publication Title
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions and its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalyzing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. Using a combination of literature information, transcription factor prediction models and genome-wide expression arrays, we inferred the regulatory network of IRG1 in mouse and human macrophages.
Publication Title
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Non-tumor-reactive T cells are characterized by the inabilitzy to lyse autologous tumor cells, low to intermediate avidity TCRs and lack of NY-ESO-1 peptide tetramer binding. However most strikingly, non-tumor-reactive T cells are characterized by a molecular program associated with division arrest anergy with elevated expression of the inhibitory molecule p27kip1. This is accompanied by elevated expression of inhibitory molecules and reduced levels of transcription factors involved in T cell activation. Frequency analysis of the inhibited T cell population using the established molecular fingerprint as a novel biomarker might be applied for cancer vaccine development and optimization.
Publication Title
Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy".
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
LPL co-deregulated genes after LPL specific siRNA knock-down
Publication Title
Lipoprotein lipase in chronic lymphocytic leukaemia - strong biomarker with lack of functional significance.
Sample Metadata Fields
Specimen part, Treatment
View Samples