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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 III) |
Sample organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing Third-party reanalysis
|
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
|
City |
Columbus |
State/province |
OH |
ZIP/Postal code |
43205 |
Country |
USA |
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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 |
Reanalysis of |
GSM4292892 |
Reanalysis of |
GSM4292893 |
Reanalysis of |
GSM4292898 |
Reanalysis of |
GSM4292899 |
Reanalysis of |
GSM4292900 |
Reanalysis of |
GSM4292901 |
Reanalysis of |
GSM4292906 |
Reanalysis of |
GSM4292907 |
Reanalysis of |
GSM4292908 |
Reanalysis of |
GSM4292909 |
Reanalysis of |
GSM4292914 |
Reanalysis of |
GSM4292915 |
Supplementary file |
Size |
Download |
File type/resource |
GSE185128_A673-714-H3K27ac_Enhancers_withSuper.bed.gz |
181.8 Kb |
(ftp)(http) |
BED |
GSE185128_A673-iEF-H3K27ac_Enhancers_withSuper.bed.gz |
210.4 Kb |
(ftp)(http) |
BED |
GSE185128_A673-iLuc-H3K27ac_Enhancers_withSuper.bed.gz |
163.5 Kb |
(ftp)(http) |
BED |
GSE185128_A673714H3K27acvsIgG10k.bw |
227.9 Mb |
(ftp)(http) |
BW |
GSE185128_A673iEFH3K27acvsIgG10k.bw |
230.8 Mb |
(ftp)(http) |
BW |
GSE185128_A673iLucH3K27acvsIgG10k.bw |
216.0 Mb |
(ftp)(http) |
BW |
GSE185128_EndovsKD_Gained_Enh.bed.gz |
21.1 Kb |
(ftp)(http) |
BED |
GSE185128_EndovsKD_Lost_Enh.bed.gz |
30.8 Kb |
(ftp)(http) |
BED |
GSE185128_EndovsKD_stable_Enh.bed.gz |
82.6 Kb |
(ftp)(http) |
BED |
GSE185128_RescuevsKD_Gained_Enh.bed.gz |
11.8 Kb |
(ftp)(http) |
BED |
GSE185128_RescuevsKD_Lost_Enh.bed.gz |
26.1 Kb |
(ftp)(http) |
BED |
GSE185128_RescuevsKD_Stable_Enh.bed.gz |
96.0 Kb |
(ftp)(http) |
BED |
GSE185128_RescuevsiEF_DEnhancers_DESeq2.txt.gz |
321.4 Kb |
(ftp)(http) |
TXT |
GSE185128_iLucVsiEF_DEnhancers_DESeq2.txt.gz |
325.1 Kb |
(ftp)(http) |
TXT |
GSE185128_peaks_A673_714_H3K27ac_fdr05_idr005_meanT50_FC8.narrowPeak.gz |
2.7 Mb |
(ftp)(http) |
NARROWPEAK |
GSE185128_peaks_A673_iEF_H3K27ac_fdr05_idr005_meanT50_FC8.narrowPeak.gz |
3.1 Mb |
(ftp)(http) |
NARROWPEAK |
GSE185128_peaks_A673_iLuc_H3K27ac_fdr05_idr005_meanT50_FC8.narrowPeak.gz |
2.5 Mb |
(ftp)(http) |
NARROWPEAK |
Processed data are available on Series record |