Affymetrix exon array data were generated from total RNA that was isolated from localized Ewing sarcoma biopsy specimens. Expression of transcript summarized data was compared to data generated from normal stem cells and normal adult tissues.
Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
EWS-FLI1 perturbs MRTFB/YAP-1/TEAD target gene regulation inhibiting cytoskeletal autoregulatory feedback in Ewing sarcoma.
Cell line, Treatment
View SamplesEwing Sarcoma (EwS) is a EWS-FLI1- fusion driven pediatric bone cancer with high metastatic potential. Cellular plasticity, typically regulated via the Rho-pathway, is a prerequisite for metastasis initiation. Here we interrogated the role of the Rho transcriptional effectors MRTFA/B in EwS. We find MRTFB transcriptional function strongly repressed by EWS-FLI1. Under EWS-FLI1-low (knock-down) conditions, MRTFB is activated and antagonizes global EWS-FLI1-dependent transcription. Furthermore, ChIP-Seq revealed strong overlaps in MRTFB and EWS-FLI1 chromatin occupation, especially for EWS-FLI1 suppressed-(anticorrelated) genes. Enrichment of TEAD binding motifs in these shared genomic binding regions, and overlapping transcriptional footprints of MRTFB and TEAD1-4 perturbation led us to propose synergy between MRTFB and TEAD in the regulation of EWS-FLI1 suppressed-anticorrelated genes. Finally, we find F-actin assembly to be already perturbed in our EwS model, F-actin polymerization is perturbed by EWS-FLI1 in our model cell line, however,but pharmacological inhibition of actin polymerization still reduced expression serum-induced expression of MRTFB/YAP-1/TEAD target genes. In summary our data support a model of indirect and direct EWS-FLI1-driven perturbation of MRTFB/YAP-1/TEAD target gene regulation . Overall design: 1. Transient si-RNA mediated knockdown of MRTFA (MKL-1), MRTFB (MKL-2) and doxycyline-induced EWS-FLI1 knockdown in A673/TR/shEF EwS cells (8 samples/replicate: 2 replicates total); 2. Combined transient knockdown of MRTFA, MRTFB and EWS-FLI1 in SK-N-MC EwS cells (4 samples/replicate: 2 replicates total); 3. Combined knockdown of TEAD1-4 by pooling si-RNA against TEAD1, TEAD2, TEAD3 and TEAD 4 combined with doxycycline-inducible EWS-FLI1 knockdown (4 samples/replicate: 8 samples total)
EWS-FLI1 perturbs MRTFB/YAP-1/TEAD target gene regulation inhibiting cytoskeletal autoregulatory feedback in Ewing sarcoma.
Cell line, Treatment, Subject
View SamplesEwing Sarcoma (EwS) is a EWS-FLI1- fusion driven pediatric bone cancer with high metastatic potential. Cellular plasticity, typically regulated via the Rho-pathway, is a prerequisite for metastasis initiation. Here we interrogated the role of the Rho transcriptional effectors MRTFA/B in EwS. We find MRTFB transcriptional function strongly repressed by EWS-FLI1. Under EWS-FLI1-low (knock-down) conditions, MRTFB is activated and antagonizes global EWS-FLI1-dependent transcription. Furthermore, ChIP-Seq revealed strong overlaps in MRTFB and EWS-FLI1 chromatin occupation, especially for EWS-FLI1 suppressed-(anticorrelated) genes. Enrichment of TEAD binding motifs in these shared genomic binding regions, and overlapping transcriptional footprints of MRTFB and TEAD1-4 perturbation led us to propose synergy between MRTFB and TEAD in the regulation of EWS-FLI1 suppressed-anticorrelated genes. Finally, we find F-actin assembly to be already perturbed in our EwS model, F-actin polymerization is perturbed by EWS-FLI1 in our model cell line, however,but pharmacological inhibition of actin polymerization still reduced expression serum-induced expression of MRTFB/YAP-1/TEAD target genes. In summary our data support a model of indirect and direct EWS-FLI1-driven perturbation of MRTFB/YAP-1/TEAD target gene regulation .
EWS-FLI1 perturbs MRTFB/YAP-1/TEAD target gene regulation inhibiting cytoskeletal autoregulatory feedback in Ewing sarcoma.
Cell line
View SamplesExpression profiles were generated from hESC-derived neural crest stem cells following transduction with GFP control vector or EWS-FLI1 vector. Expression was analyzed in stem cell conditions 5 days after transduction (undifferentiated conditions) and after 6 weeks in differentiation media (differentiation conditions).
Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.
Specimen part, Treatment
View SamplesExpression profiling of MRC5, IFN gamma treated MRC5 and PGF cells.
Reconfiguration of genomic anchors upon transcriptional activation of the human major histocompatibility complex.
No sample metadata fields
View SamplesCaspases are cysteine-proteases with key roles in the execution phase of apoptosis. Additional cellular activities, unrelated to cell death seem to be influenced by these enzymes. Identification of genes co-regulated with caspases could help to ascertain new biological roles for these proteases.To identify genes and pathways under the influence of caspase-2 we silenced its expression in U87MG glioblastoma cell line. Transcriptional expression profiles of cells transfected with caspase-2 siRNA or control siRNA were compared.
Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain.
Cell line, Treatment
View SamplesWe sought to find a gene-expression multigene predictor of response to infliximab therapy in Rheumatoid Arthritis patients. Using internal and external cross-validation systems we have built and validated an 8-gene predictor for response to infliximab.
An eight-gene blood expression profile predicts the response to infliximab in rheumatoid arthritis.
Sex, Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA networks in mouse lung organogenesis.
Sex
View Samples