ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3.

ABSTRACT: The mechanistic basis for the metastasis of Ewing sarcomas remains poorly understood, as these tumors harbor few mutations beyond the chromosomal translocation that initiates the disease. Instead, the epigenome of Ewing sarcoma 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 EWSR1::FLI1/ERG's repression of transcription factor genes, concentrating on those that exhibit a broader range of expression in tumors than in Ewing sarcoma cell lines. Focusing on one of these target genes, ETS1, we detected EWSR1::FLI1 binding and an H3K27me3-repressive mark at this locus. Depletion of EWSR1::FLI1 results in ETS1's binding of promoter regions, substantially altering the transcri

SUBMITTER: Ebegboni VJ 

PROVIDER: S-EPMC11219265 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature