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Series GSE92738 Query DataSets for GSE92738
Status Public on Jul 06, 2017
Title EWS-FLI1 represses Rho-actin signaling via MRTFB/YAP-1/TEAD perturbation in Ewing Sarcoma [Chip-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Ewing 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 Chromatin Immunoprecipitation coupled with Next-generation sequencing (ChIP-seq) of MRTFA, MRTFB, SRF and EWS-FLI1 (2 replicates each) under serum-induced conditions.
Contributor(s) Katschnig AM, Kauer MO, Schwentner R, Tomazou EM, Mutz CN, Linder M, Sibilia M, Alonso J, Aryee DN, Kovar H
Citation(s) 28671673
Submission date Dec 22, 2016
Last update date May 15, 2019
Contact name Maximilian Kauer
Organization name CCRI, St.Anna Children Cancer Research Institute
Department Molecular Biology
Lab Heinrich Kovar
Street address Zimmermannplatz 10
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (10)
GSM2436676 A673/TR/shEF_FLI1_ChIP_nodox_rep1
GSM2436677 A673/TR/shEF_FLI1_ChIP_nodox_rep2
GSM2436678 A673/TR/shEF_SRF_ChIP_nodox_rep1
This SubSeries is part of SuperSeries:
GSE92741 EWS-FLI1 represses Rho-actin signaling via MRTFB/YAP-1/TEAD perturbation in Ewing Sarcoma
BioProject PRJNA358640
SRA SRP095612

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Supplementary file Size Download File type/resource
GSE92738_RAW.tar 13.0 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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