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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 15, 2024 |
| Title |
EWSR1::FLI1 fusion oncoproteins’ regulation of ETS1 (ChIP-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Ewing sarcomas harbor few mutations beyond the chromosomal translocation that initiates disease and the mechanistic basis for the metastasis of these tumors remains poorly understood. The epigenome of Ewing sarcoma (EWS) cells reflects the regulatory state of genes associated with the DNA binding activity of the fusion oncoproteins EWSR1::FLI1 or EWSR1::ERG. In this study, we examined the repressive activities of the EWSR1::FLI1/ERG fusion oncoproteins. Focusing on one of the repressed EWSR1::FLI1/ERG target genes, ETS1, we detected EWSR1::FLI1 binding and a H3K27me3 repressive mark at this locus. Depletion of EWSR1::FLI1 results in ETS1’s binding of promoter regions, and we show ETS1 regulates the expression of multiple proteins that function in extracellular matrix organization including TENSIN3 (TNS3). Interestingly, TNS3 expression in EWS tumors significantly correlates with that of ETS1 (0.85, FDR <0.01). TNS3 is a focal adhesion protein that contributes to tumor cell migration by connecting the cytoplasmic tail of integrins to the actin cytoskeleton. EWS cell lines, in which we activated ETS1 expression (CRISPRa) exhibited increased TNS3 expression and a migratory phenotype. Critically, the activated ETS1 EWS cell lines show TNS3 accumulation at leading cell edges, with F-actin cytoskeletal reorganization, a phenotype associated with cell migration.
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| Overall design |
Ewing sarcoma cell line (TC-32) was analyzed by ChIP-seq. EWSR1::FLI1 was depleted by transfection with siRNA (siFLI1 and siNeg control).
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| Web link |
https://aacrjournals.org/mcr/article/22/7/625/746058/ETS1-a-Target-Gene-of-the-EWSR1-FLI1-Fusion
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| Contributor(s) |
Caplen NJ, Ebegboni VJ |
| Citation(s) |
38588446, 38187702 |
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| Submission date |
Sep 13, 2023 |
| Last update date |
Jul 15, 2024 |
| Contact name |
Natasha J Caplen |
| Organization name |
National Institutes of Health
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| Department |
National Cancer Institute
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| Lab |
Functional Genetics
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| Street address |
37 Convent Drive, Bldg. 37, Rm 6128
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| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
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| Samples (22)
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| GSM7780179 |
TC-32 siNEG, ETS1, rep 2 |
| GSM7780180 |
TC-32 siFLI1, Input, rep 1 |
| GSM7780181 |
TC-32 siFLI1, Input, rep 2 |
| GSM7780182 |
TC-32 siFLI1, ETS1, rep 1 |
| GSM7780183 |
TC-32 siFLI1, ETS1, rep 2 |
| GSM7780184 |
TC-32 siNEG, Input, rep 1_I |
| GSM7780185 |
TC-32 siNEG, Input, rep 2_II |
| GSM7780186 |
TC-32 siNEG, H3K27ac, rep 1_I |
| GSM7780187 |
TC-32 siNEG, H3K27ac, rep 2_II |
| GSM7780188 |
TC-32 siNEG, H3K4me3, rep 1 |
| GSM7780189 |
TC-32 siNEG, H3K4me3, rep 2 |
| GSM7780192 |
TC-32 siFLI1, Input, rep 1_I |
| GSM7780193 |
TC-32 siFLI1, Input, rep 2_II |
| GSM7780194 |
TC-32 siFLI1, H3K27ac, rep 1 |
| GSM7780195 |
TC-32 siFLI1, H3K27ac, rep 2 |
| GSM7780196 |
TC-32 siFLI1, H3K4me3, rep 1 |
| GSM7780197 |
TC-32 siFLI1, H3K4me3, rep 2 |
| GSM7980901 |
TC-32 siNEG, H3K27ac, rep 1a |
| GSM7980902 |
TC-32 siFLI1, H3K27ac, rep 1a |
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| This SubSeries is part of SuperSeries: |
| GSE243184 |
ETS1, a target gene of the EWSR1::FLI1 fusion oncoprotein, regulates the expression of the focal adhesion protein TENSIN3 |
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| Relations |
| BioProject |
PRJNA1016476 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE243171_RAW.tar |
9.5 Mb |
(http)(custom) |
TAR (of NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
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