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Series GSE243277 Query DataSets for GSE243277
Status Public on Apr 15, 2024
Title EWSR1::FLI1 fusion oncoproteins’ regulation of ETS1 (CUT&RUN)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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 (TSN3). Interestingly, TSN3 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.
Overall design We assessed EWSR1::FLI1’s associations with distinct epigenetic states. Using samples generated from TC-32 cells, we employed CUT&RUN to determine EWSR1::FLI1 binding sites and mapped histone modifications associated with transcriptional activation, H3K27ac, and repression, H3K9me3 and H3K27me3
Contributor(s) Caplen NJ, Ebegboni VJ
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Submission date Sep 14, 2023
Last update date Apr 16, 2024
Contact name Natasha J Caplen
Organization name National Institutes of Health
Department National Cancer Institute
Lab Functional Genetics
Street address 37 Convent Drive, Bldg. 37, Rm 6128
City Bethesda
State/province Maryland
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (14)
GSM7782750 TC-32 WT, A, IgG, rep 1
GSM7782751 TC-32 WT, A, IgG, rep 2
GSM7782752 TC-32 WT, A, FLI1, rep 1
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
BioProject PRJNA1017516

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Supplementary file Size Download File type/resource
GSE243277_RAW.tar 1.8 Gb (http)(custom) TAR (of BED, BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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