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Series GSE83724 Query DataSets for GSE83724
Status Public on Apr 27, 2017
Title PAX3-FOXO1 requires BRD4 to drive oncogene addiction in RMS cells [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The fusion transcription factor PAX3-FOXO1 drives oncogenesis in a subset of rhabdomyosarcomas, however the mechanisms by which it remodels chromatin are unknown. We find PAX3-FOXO1 reprograms the cis-regulatory landscape by inducing super enhancers (SEs), in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors. Deregulation of PAX3-FOXO1 itself occurs by translocation-induced chromatin loops bringing the PAX3 promoter under the control of FOXO1 enhancers. Protein targets induced by, or bound to, PAX3-FOXO1 occupied SEs, were selectively sensitive to small molecule inhibition. PAX3-FOXO1 co-binds BRD4 at SEs, and BET bromodomains are required for PAX3-FOXO1-dependent transcription and cancer cell growth.
Overall design RNA-seq in FP-RMS cells exposed to either DMSO or JQ1 treatment, and RNA-seq of fibroblast cells stably transduced with either empty vector or PAX3-FOXO1 vector.
Contributor(s) Gryder BE, Wen X
Citation(s) 28446439, 32744500
Submission date Jun 26, 2016
Last update date May 06, 2021
Contact name Javed Khan
Phone 2407606135
Organization name NCI, NIH
Department Genetics Branch
Lab Javed Khan
Street address 37 Convent Dr.
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (10)
GSM2214061 7250-empty RNA-seq
GSM2214062 7250-PAX3-FOXO1 RNA-seq
GSM2214063 RH4 JQ1 500nM 6hr RNA-seq
This SubSeries is part of SuperSeries:
GSE83728 Epigenetic Lanscape and BRD4 Transcriptional Dependency of PAX3-FOXO1 Driven Rhabdomyosarcoma
BioProject PRJNA326875
SRA SRP077230

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Supplementary file Size Download File type/resource
GSE83724_RAW.tar 7.9 Mb (http)(custom) TAR (of FPKM_TRACKING)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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