GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE92nnn/GSE92738/primaryOK2000000GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE92738GEOGSE0falseEWS-FLI1 represses Rho-actin signaling via MRTFB/YAP-1/TEAD perturbation in Ewing Sarcoma [Chip-Seq]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 .2017/07/06GSE92738GSM2436677GSM2436678GSM2436679GSM2436684GSM2436685GSM2436676GSM2436680GSM2436681GSM2436682GSM243668311154SRP09561292738Homo sapiens[28671673]