The DBD-α4 helix of EWSR1::FLI1 is required for GGAA microsatellite binding that underlies genome regulation in Ewing sarcoma
- Center for Childhood Cancer, Abigail Wexner Research Institute at Nationwide Children’s Hospital, United States
- Medical Scientist Training Program, The Ohio State University, United States
- Biomedical Sciences Graduate Program, The Ohio State University, United States
- Ohio State Biochemistry Program, United States
- Department of Pediatrics, The Ohio State Univeristy, United States
- Division of Pediatric Heme/Onc/BMT, The Ohio State University College of Medicine, United States
Figures
Figure 1 with 4 supplements
The DBD-α4 helix of FLI1 domain is required to restructure chromatin in A-673 cell.
(A) A schematic of DBD and DBD+ constructs used in shRNA knockdown and rescue experiments. (B) Multidimensional scaling (MDS) plot of top 1000 interactions (500 kb resolution) in each biological replicate. (C) Genome-wide interaction frequency (ICE-corrected Micro-C counts) over genomic distance (bp) at 5 kb resolution. (D) Volcano plot showing differentially interacting regions (DIRs) detected at 500 kb resolution for DBD+ replicates versus KD replicates. (E) Volcano plot showing DIRs detected at same resolution for DBD replicates versus KD replicates. Boxplots depict the minimum, first quartile, median, third quartile, and maximum. *p-Value<0.05, p-value<0.001.
Figure 1—figure supplement 1
DBD-a4 helix of FLI1 domain is required for EWSR1::FLI1-driven transcriptional regulation and oncogenic transformation in A-673 cells.
(A) The DBD-α4 helix of FLI1 depicted on dsDNA (PDB). (B) Knockdown of endogenous EWSR1::FLI1 detected with FLI1 ab and rescue of wtEF, DBD, and DBD+ detected with FLAG ab in A-673 cells. (C) A principal component analysis (PCA) plot of RNA-seq experiments in A-673 cells. (D) Representative image of soft agar colony plates and quantification of three biological replicates. Bar charts display mean and standard deviation.
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Figure 1—figure supplement 1—source data 1
PDF file containing original western blots for Figure 1—figure supplement 1B, indicating the relevant bands and treatments.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp1-data1-v1.zip
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Figure 1—figure supplement 1—source data 2
Original files for western blot analysis displayed in Figure 1—figure supplement 1B.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp1-data2-v1.zip
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Figure 1—figure supplement 1—source data 3
PDF files containing original agar gels for Figure 1—figure supplement 1D, indicating the technical replicates and treatments.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp1-data3-v1.zip
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Figure 1—figure supplement 1—source data 4
Original files for agar gels displayed in Figure 1—figure supplement 1D.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp1-data4-v1.zip
Figure 1—figure supplement 2
Genome-wide Micro-C interaction frequency profiles across biological replicates in A-673 cells.
(A) Genome-wide interaction frequency (ICE-corrected Micro-C counts) over genomic distance (bp) at 5 kb resolution for replicate 1 of A-673. (B) Genome-wide interaction frequency (ICE-corrected Micro-C counts) over genomic distance (bp) at 5 kb resolution for replicate 2 of A-673.
Figure 1—figure supplement 3
DBD-a4 helix of FLI1 domain is required for EWSR1::FLI1-driven transcriptional regulation and oncogenic transformation in TTC-466 cells.
(A) Knockdown of endogenous EWSR1::ERG detected with ERG ab and rescue of wtEF, DBD, and DBD+ detected with FLAG ab in TTC-466 cells. (B) A principal component analysis (PCA) plot of RNA-seq experiments in TTC-466 cells. (C) Representative images of soft agar colony plates.
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Figure 1—figure supplement 3—source data 1
PDF file containing original western blots for Figure 1—figure supplement 3A, indicating the relevant bands and treatments.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp3-data1-v1.zip
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Figure 1—figure supplement 3—source data 2
Original files for western blot analysis displayed in Figure 1—figure supplement 3A.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp3-data2-v1.zip
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Figure 1—figure supplement 3—source data 3
PDF files containing original agar gels for Figure 1—figure supplement 3C, indicating the technical replicates and treatments.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp3-data3-v1.zip
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Figure 1—figure supplement 3—source data 4
Original files for agar gels displayed in Figure 1—figure supplement 3C.
- https://cdn.elifesciences.org/articles/95626/elife-95626-fig1-figsupp3-data4-v1.zip
Figure 1—figure supplement 4
DBD-a4 helix of FLI1 domain is required to restructure chromatin in TTC-466 cells.
(A) Multidimensional scaling (MDS) plot of top 1000 interactions (500 kb resolution) in each biological replicate. (B) Genome-wide interaction frequency of combined replicates (ICE-corrected Micro-C counts) over genomic distance (bp) at 5 kb resolution. (C) Volcano plot showing differentially interacting regions (DIRs) detected at 500 kb resolution for DBD+ replicates versus KD replicates. (D) Volcano plot showing DIRs detected at same resolution for DBD replicates versus KD replicates.
Figure 2 with 2 supplements
Altered topologically associated domain (TAD) structure in A-673 DBD cells is linked to GGAA microsatellite binding.
(A) Number of TADs detected in DBD and DBD+ compared to KD at resolutions of 10 kb, 25 kb, 50 kb, and 100 kb. (B) Proportion of TADs (compared to KD) bound by FLAG, CTCF, both, or neither. (C) Venn diagram of overlap between DBD and DBD+ TADs (compared to KD). (D–H) Comparison of DBD and DBD+ unique TADs. (D) Binding intensity of unique FLAG peaks (FDR<0.05, FC>8, counts>80, IDR<0.01) across the width of DBD and DBD+ unique TADs. (E) Width of DBD and DBD+ unique TADs in bp. (F) Expression level of significantly upregulated genes within unique TADs in DBD and DBD+ bound by FLAG. (G) Length of microsatellites bound by unique FLAG peaks in DBD and DBD+ conditions in bp. (H) Density of GGAA motif in the microsatellites calculated as (# of motif × 4)/(length of microsatellites) in DBD and DBD+ unique TADs bound by unique FLAG peaks. Boxplots depict the minimum, first quartile, median, third quartile, and maximum. p-Value<0.001.
Figure 2—figure supplement 1
DBD-a4 helix of FLI1 domain influences topologically associated domain (TAD) boundary formation, GGAA microsatellite occupancy, and associated transcriptional regulation in A-673 cells.
(A) Expression level of significant genes overlapped with unique topologically associated domains (TADs) in DBD (mean = −0.64) and DBD+ (mean = −1.16) bound by FLAG at GGAA microsatellites. (B) Proportion of TAD boundaries bound by FLAG, CTCF, or neither. (C–G) Comparison of DBD and DBD+ unique TAD boundaries. (C) Binding intensity of unique FLAG peaks (FDR<0.05, FC>8, counts>80, IDR<0.01) at boundaries of DBD and DBD+ unique TADs. (D) Expression level of significantly upregulated genes overlapped with boundaries of unique TADs in DBD and DBD+ bound by FLAG at GGAA microsatellites. (E) Expression level of significantly downregulated genes overlapped with boundaries of unique TADs in DBD and DBD+ bound by FLAG at GGAA microsatellites. (F) Length of microsatellites bound by unique FLAG peaks at the boundaries of DBD and DBD+ conditions in bp. (G) Percent of GGAA motif in the microsatellites calculated as (# of motif × 4)/(length of microsatellites) at the boundaries of DBD and DBD+ unique TADs bound by unique FLAG peaks. All data are from A-673 cells. Boxplots depict the minimum, first quartile, median, third quartile, and maximum. p-Value<0.001.
Figure 2—figure supplement 2
Topologically associated domain (TAD) analysis in TTC-466 cells.
(A) Number of TADs detected in DBD and DBD+ compared to KD at resolutions of 10 kb, 25 kb, 50 kb, and 100 kb. (B) Venn diagram of overlap between DBD and DBD+ TADs (compared to KD).
Figure 3 with 2 supplements
DBD and DBD+ form loops at GGAA microsatellites, but DBD+ rescues more and shorter loops in A-673 cells.
(A) Number of loops detected in DBD and DBD+ compared to KD at resolutions of 1 kb at short-range (<50 kb), mid-range (50–500 kb), and long-range (>500 kb). (B) Venn diagram of overlap between DBD and DBD+ uniquely gained loops (compared to KD). (C) Expression level of significant genes overlapped with uniquely gained loop anchors of DBD and DBD+. Means = 0.45 (DBD) and 0.77 (DBD+). (D) Peak intensity of unique FLAG peaks (FDR<0.05, FC>8, counts>80, IDR<0.01) at anchors of uniquely gained loops in DBD and DBD+ cells. Means = 5.01 and 6.30 per DBD and DBD+. (E) Length of microsatellites bound by unique FLAG peaks at the anchors of DBD and DBD+ uniquely gained loops in bp. Means = 22.5 bp (DBD) and 38 bp (DBD+). (F) Density of GGAA motif in the microsatellites calculated as (# of motif × 4)/(length of microsatellites) at the anchors of DBD and DBD+ uniquely gained loops bound by unique FLAG peaks. Means = 0.51 (DBD) and 0.70 (DBD+). Boxplots depict the minimum, first quartile, median, third quartile, and maximum. *p-Value<0.05, p-value<0.001.
Figure 3—figure supplement 1
DBD+ loop anchors associated with more gene down regulation compared to DBD specific anchors.
(A) Venn diagram of overlap between DBD and DBD+ uniquely lost loops (compared to KD). (B) Expression level of downregulated genes overlapped with uniquely gained loop anchors of DBD and DBD+. All data are from A-673 cells. Means = –0.68, –1.25, 0.35, –1.08. p-Value<0.05, p-value<0.001. Boxplots depict the minimum, first quartile, median, third quartile, and maximum.
Figure 3—figure supplement 2
Loop analysis in TTC-466 cells.
(A) Number of loops detected in DBD and DBD+ compared to KD at resolutions of 1 kb at short-range (<50 kb), mid-range (50–500 kb), and long-range (>500 kb). (B) Venn diagram of overlap between DBD and DBD+ uniquely gained loops (compared to KD). (C) Venn diagram of overlap between DBD and DBD+ uniquely lost loops (compared to KD).
Figure 4 with 2 supplements
DBD+ rescues de novo enhancer formation at microsatellites A-673 cells.
(A) Principal component analysis (PCA) plot of H3K27ac peaks in biological replicates of KD, DBD, and DBD+. (B) Venn diagram of overlap of H3K27ac peaks (FDR<0.05, FC>8, counts>80, IDR<0.01) between DBD and DBD+. (C) Percentage of H3K27ac peaks at microsatellites in common, DBD unique, and DBD+ unique peaks. (D) Number of H3K27ac peaks constituting typical and super-enhancers called in DBD and DBD+ conditions. (E) Constituent size (in bp) of typical and super-enhancers in DBD and DBD+ conditions. (F) Expression level of significantly upregulated genes at DBD and DBD+ super-enhancers. Boxplots depict the minimum, first quartile, median, third quartile, and maximum. Circles depict outliers. p-Value<0.001.
Figure 4—figure supplement 1
DBD-α4 helix of FLI1 induces stronger gene deactivation at DBD+ super-enhancer compared to DBD super -enhancers in A-673 cells.
(A) Expression level of downregulated genes at DBD and DBD+ super-enhancers in A-673 cells. p-Value<0.001. Boxplots depict the minimum, first quartile, median, third quartile, and maximum.
Figure 4—figure supplement 2
H3K27ac CUT&Tag analysis in TTC-466 cells.
Principal component analysis (PCA) plot of H3K27ac peaks in biological replicates of KD, DBD, and DBD+.
Figure 5 with 1 supplement
DBD-α4 helix of FLI1 promotes binding at longer and denser GGAA microsatellites in A-673 cells.
(A) Venn diagram of overlap between FLAG peaks (FDR<0.05, FC>8, counts>80, IDR<0.01) of DBD and DBD+ cells. (B) Percentage of FLAG peaks bound at microsatellites in common, DBD unique, and DBD+ unique peaks. (C) Intensity of peaks in DBD unique (mean = 5.75), DBD common (mean = 7.76), DBD+ common (mean = 7.75), and DBD+ unique (mean = 6.83) FLAG peaks. (D) Length (in bp) of GGAA microsatellites bound by DBD unique (mean = 36.61), common in both (mean = 50.94), and DBD+ unique (mean = 43.25) FLAG peaks. (E) Total number of GGAA motifs in microsatellites bound by DBD unique (mean = 4.66), common in both (mean = 8.70), and DBD+ unique (mean = 7.78) FLAG peaks. (F) Maximum consecutive number of GGAA motifs in microsatellites bound by DBD unique (mean = 1.48), common in both (mean = 5.21), and DBD+ unique (mean = 5.32) FLAG peaks. (G) Percentage of GGAA motif in the microsatellites calculated as (# of motif × 4)/(length of microsatellites) bound by DBD unique (mean = 0.54), common in both (mean = 0.65), and DBD+ unique (mean = 0.69) FLAG peaks. (H) Maximum number of insertion (gaps in bp) in microsatellites bounds by DBD unique (mean = 10.1), common (mean = 9.1), and DBD+ unique (mean = 8.3) FLAG peaks. Boxplots depict the minimum, first quartile, median, third quartile, and maximum. p-Value<0.05, p-value<0.01, and p-value<0.001.
Figure 5—figure supplement 1
FLAG CUT&Tag analysis in TTC-466 cells.
(A) Venn diagram of overlap between FLAG peaks (FDR<0.05, FC>8, counts>80, IDR<0.01) of DBD and DBD+ cells. (B) Percentage of FLAG peaks bound at microsatellites in common, DBD unique, and DBD+ unique peaks. (C) Length (in bp) of GGAA microsatellites bound by DBD unique (mean = 30.28), common in both (mean = 37.79), and DBD+ unique (mean = 22.74) FLAG peaks. (D) Total number of GGAA motifs in microsatellites bound by DBD unique (mean = 3.70), common in both (mean = 6.05), and DBD+ unique (mean = 3.00) FLAG peaks. (E) Maximum consecutive number of GGAA motifs in microsatellites bound by DBD unique (mean = 1.35), common in both (mean = 3.44), and DBD+ unique (mean = 1.57v) FLAG peaks. (F) Percentage of GGAA motif in the microsatellites calculated as (# of motif × 4)/(length of microsatellites) bound by DBD unique (mean = 0.53), common in both (mean = 0.60), and DBD+ unique (mean = 0.54) FLAG peaks. (G) Maximum number of insertion (gaps in bp) in microsatellites bound by DBD unique (mean = 10.0), common (mean = 9.36), and DBD+ unique (mean = 9.77) FLAG peaks. Boxplots depict the minimum, first quartile, median, third quartile, and maximum. p-Value<0.05, p-value<0.01, and p-value<0.001.
Figure 6 with 15 supplements
The DBD-α4 helix promotes formation of transcription hubs by effective binding at microsatellites.
(A) 250 kb region on chr 19 containing FCGRT and other genes. Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD and DBD+/KD). Uniquely gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Enhancers and super-enhancers are shown as green bars. Gene expression is in black tracks. (B) FCGRT promoter region containing GGAA microsatellites. (C) NOSIP promoter region containing GGAA repeats. (D) Model of EWSR1::FLI1-driven transcription hub.
Figure 6—figure supplement 1
CCND1 hub in 700 kb region on chr 11 in A-673 DBD cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD). Uniquely gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Enhancers and super-enhancers are shown as green bars. Gene expression is in black tracks.
Figure 6—figure supplement 2
CCND1 hub in 700 kb region on chr 11 in A-673 DBD+ cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD+/KD). Uniquely gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Enhancers and super-enhancers are shown as green bars. Gene expression is in black tracks.
Figure 6—figure supplement 3
NKX2-2 hub on chr 20 in A-673 DBD cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD). Uniquely gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Enhancers and super-enhancers are shown as green bars. Gene expression is in black tracks.
Figure 6—figure supplement 4
NKX2-2 hub on chr 20 in A-673 DBD+ cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD+/KD). Uniquely gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Enhancers and super-enhancers are shown as green bars. Gene expression is in black tracks.
Figure 6—figure supplement 5
GSTM4 hub chr 1 in A-673 DBD cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD). Uniquely gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Enhancers and super-enhancers are shown as green bars. Gene expression is in black tracks.
Figure 6—figure supplement 6
GSTM4 hub chr 1 in A-673 DBD+ cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD+/KD). Uniquely gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Enhancers and super-enhancers are shown as green bars. Gene expression is in black tracks.
Figure 6—figure supplement 7
FCGRT hub in 250 kb region on chr 19 in TTC-466 DBD cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 8
FCGRT hub in 250 kb region on chr 19 in TTC-466 DBD+ cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD+/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 9
CCND1 hub in 700 kb region on chr 11 in TTC-466 DBD cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 10
CCND1 hub in 700 kb region on chr 11 in TTC-466 DBD+ cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD+/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 11
NKX2-2 hub chr 20 in TTC-466 DBD cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 12
NKX2-2 hub on chr 20 in TTC-466 DBD+ cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD+/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 13
GSTM4 hub chr 1 in TTC-466 DBD cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 14
GSTM4 hub on chr 1 in TTC-466 DBD+ cells.
Topologically associated domains (TADs) are depicted on 1 kb matrices (DBD+/KD). Gained loops are shown as red inverted arcs. FLAG CUT&Tag bigwig tracks depicted in magenta. GGAA microsatellites in hg19. CTCF CUT&Tag track is in blue middle row. H3K27ac tracks are in green. Gene expression is in black tracks.
Figure 6—figure supplement 15
A-673 and TTC-466 cell line comparison.
(A) Principal component analysis (PCA) plot of RNA-Seq replicates of A-673 and TTC-466 cells. (B) Sequencing depth of Micro-C replicates of A-673 cells. (C) Sequencing depth of Micro-C replicates of TTC-466 cells.
Author response image 1
Expression Levels of DBD and DBD+ Across Experiments.
Expression levels of DBD and DBD+ protein based on western blot band intensity normalized by tubulin band intensity. Expression levels are relative to wildtype EWSR1::FLI1 rescue levels and are calculated for (A) A673 samples used for micro-C and (B) all published studies of DBD and DBD+. Data show mean and standard deviation for samples. P-values were calculated with an unpaired t-test.
Author response image 2
CHX chase assay to determine the stability of DBD and DBD+.
(A) Knock-down of endogenous EWSR1::FLI1 detected with FLI1 ab and rescue with DBD and DBD+ detected with FLAG ab. (B) CHX chase assay to determine the stability of DBD and DBD+ in A-673 cells with quantification of the protein levels (n=3). Error bars represent standard deviation. The half-lives (t1/2) of DBD and DBD+ were listed in the table.
Tables
Table 1
Differential expression of FCGRT hub genes in DBD and DBD+ compared to KD.
| Gene symbol | DBD FC | DBD padj | DBD+ FC | DBD+ padj |
|---|---|---|---|---|
| ALDH16A1 | 1.207 | 0.046 | 1.107 | 0.329 |
| RPL13A | –1.132 | 0.0214 | –1.209 | 7.46E-05 |
| RPL13AP5 | –1.109 | 0.491 | –1.149 | 0.291 |
| RPS11 | –1.068 | 0.337 | –1.177 | 0.002 |
| FCGRT | 1.639 | 2.14E-4 | 2.44 | 2.54E-13 |
| RCN3 | –1.588 | 6.85E-06 | –1.406 | 9.58E-4 |
| NOSIP | 1.065 | 0.447 | –1.041 | 0.637 |
| PRRG2 | 1.117 | 0.760 | –1.042 | 0.917 |
| PRR12 | 1.177 | 0.007 | 1.088 | 0.204 |
| RRAS | –1.655 | 1.63E-17 | –1.383 | 5.10E-08 |
| SCAF1 | 1.065 | 0.357 | –1.07 | 0.283 |
| IRF3 | 1.081 | 0.402 | 1.196 | 0.0115 |
| BCL2L12 | 1.255 | 0.007 | 1.359 | 6.60E-05 |
| PRMT1 | 1.151 | 0.015 | 1.145 | 0.015 |
| ADM5 | 1.122 | 0.740 | 1.064 | 0.864 |
Additional files
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MDAR checklist
- https://cdn.elifesciences.org/articles/95626/elife-95626-mdarchecklist1-v1.docx
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Source code 1
Source code for sequencing data analysis.
- https://cdn.elifesciences.org/articles/95626/elife-95626-code1-v1.zip
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The DBD-α4 helix of EWSR1::FLI1 is required for GGAA microsatellite binding that underlies genome regulation in Ewing sarcoma
eLife 13:RP95626.
https://doi.org/10.7554/eLife.95626.4
