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Status |
Public on Aug 15, 2022 |
Title |
EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma (CUT&Tag II) |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
Ewing sarcoma is a prototypical fusion transcription factor-associated pediatric cancer that expresses EWS/FLI or highly related fusions. EWS/FLI dysregulates transcription to induce and maintain sarcomagenesis, but the mechanisms utilized are not fully understood. We therefore sought to define the global effects of EWS/FLI on chromatin conformation and transcription in Ewing sarcoma. We found that EWS/FLI (and EWS/ERG) genomic localization is largely conserved across multiple patient-derived Ewing sarcoma cell lines. EWS/FLI binding is primarily associated with compartment activation, establishment of topologically-associated domain (TAD) boundaries, enhancer-promoter looping that involve both intra- and inter-TAD interactions, and gene activation. Importantly, local chromatin features provide the basis for transcriptional heterogeneity in regulation of direct EWS/FLI target genes across different Ewing sarcoma cell lines. These data demonstrate a key role of EWS/FLI in mediating genome-wide changes in chromatin configuration and support the notion that fusion transcription factors serve as master regulators through three-dimensional reprogramming of chromatin.
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Overall design |
EWS/FLI knock-down with RNAi followed by rescue of EWS/FLI expression with a 3XFLAG tagged EWS/FLI cDNA construct
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Contributor(s) |
Showpnil IA, Lessnick SL |
Citation(s) |
36124657 |
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Submission date |
Sep 30, 2021 |
Last update date |
Oct 26, 2022 |
Contact name |
Iftekhar Ahmed Showpnil |
E-mail(s) |
[email protected]
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Organization name |
Nationwide Children's Hospital
|
Department |
CCCBD
|
Lab |
Lessnick
|
Street address |
700 Childrens Drive
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City |
Columbus |
State/province |
OH |
ZIP/Postal code |
43205 |
Country |
USA |
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Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (20)
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This SubSeries is part of SuperSeries: |
GSE185132 |
EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma |
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Relations |
BioProject |
PRJNA767689 |
SRA |
SRP339579 |
Supplementary file |
Size |
Download |
File type/resource |
GSE185127_A673714log2CTCFvsIgG10.bw |
204.5 Mb |
(ftp)(http) |
BW |
GSE185127_A673ieflog2CTCFvsIgG10.bw |
201.0 Mb |
(ftp)(http) |
BW |
GSE185127_A673iluclog2CTCFvsIgG10.bw |
171.1 Mb |
(ftp)(http) |
BW |
GSE185127_CTCF_KDb_peaks_uniq.bed.gz |
1.1 Kb |
(ftp)(http) |
BED |
GSE185127_CTCF_WTb_peaks_uniq.bed.gz |
1.0 Kb |
(ftp)(http) |
BED |
GSE185127_CTCF_stableb_peaks_uniq.bed.gz |
31.0 Kb |
(ftp)(http) |
BED |
GSE185127_Surdezetal2021_A673_WT_Input_sorted_dedup.bw |
420.1 Mb |
(ftp)(http) |
BW |
GSE185127_Surdezetal2021_A673_WT_Rad21_sorted_dedup.bw |
311.9 Mb |
(ftp)(http) |
BW |
GSE185127_Surdezetal2021_A673_WT_SMC1A_sorted_dedup.bw |
329.6 Mb |
(ftp)(http) |
BW |
GSE185127_TC71ieflog2CTCFvsIgG10.bw |
154.6 Mb |
(ftp)(http) |
BW |
GSE185127_TC71iluclog2CTCFvsIgG10.bw |
139.9 Mb |
(ftp)(http) |
BW |
GSE185127_peaks_A673_iEF_197_CTCF.narrowPeak.gz |
666.1 Kb |
(ftp)(http) |
NARROWPEAK |
GSE185127_peaks_A673_iEF_714_CTCF.narrowPeak.gz |
680.3 Kb |
(ftp)(http) |
NARROWPEAK |
GSE185127_peaks_A673_iLuc_197_CTCF.narrowPeak.gz |
656.5 Kb |
(ftp)(http) |
NARROWPEAK |
GSE185127_peaks_TC71_iEF_CTCF.narrowPeak.gz |
681.8 Kb |
(ftp)(http) |
NARROWPEAK |
GSE185127_peaks_TC71_iLuc_CTCF.narrowPeak.gz |
677.2 Kb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |