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Series GSE87324 Query DataSets for GSE87324
Status Public on Mar 09, 2018
Title BRCA1/RNApII regulation in Ewing's sarcoma (ChIP-seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Ewing sarcoma (EwS) is an aggressive pediatric bone and soft tissue cancer. It is driven by a fusion oncogene involving the EWSR1 gene, predominantly EWS-FLI1. EwS is exquisitely sensitive to genotoxic agents, but the molecular basis for this sensitivity is relatively underexplored. We have discovered that EwS displays alterations in damage-induced transcription regulation and an accumulation of R-loops. Consequently, we observe an increase in replication stress but impaired homologous recombination. We demonstrate an enriched interaction between BRCA1 and the elongating transcription machinery and suggest that this interaction may be the underlying cause for impaired recombination. Investigation into the unique transcription profile of EwS also revealed upregulated mechanisms (including RNASEH2, FEN1 and Fanconi Anemia pathway) to compensate for the increased EWS-FLI1 induced toxicity. Finally, we have uncovered a novel role for EWSR1 transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Taken together, our findings improve the current understanding of wild-type EWSR1 function, elucidate the mechanistic basis for EwS chemosensitivity (including PARP1 inhibitors) and suggest potential targets for novel second-line therapy.
 
Overall design Four different cell lines, IMR90, U2OS, TC32 and EWS502 were profiled for RNAPII and BRCA1 via ChIP protocol. Samples treated with etoposide for 6 hours were profiled as well.
 
Contributor(s) Gorthi A, Yidong C, Bishop AJ
Citation(s) 29513652
Submission date Sep 23, 2016
Last update date May 15, 2019
Contact name Yidong Chen
E-mail(s) cheny8@uthscsa.edu
Phone 2105629163
Organization name UT Health Science Center at San Antonio
Department Epidemiology and Biostatistics
Street address 8403 Floyd Curl Drive, MSC 7784
City San Antonio
State/province Texas
ZIP/Postal code 78229
Country USA
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (26)
GSM2327769 TC32 NT RNAPII
GSM2327770 TC32 Etop RNPII
GSM2327771 TC32 NT BRCA1
This SubSeries is part of SuperSeries:
GSE68847 BRCA1, R-loops and Recombination defects in Ewing's sarcoma
Relations
BioProject PRJNA344334
SRA SRP090392

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE87324_RAW.tar 4.4 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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