STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.

ABSTRACT: Cohesin complexes carrying STAG1 or STAG2 organize the genome into chromatin loops. STAG2 loss-of-function mutations promote metastasis in Ewing sarcoma, a pediatric cancer driven by the fusion transcription factor EWS::FLI1. We integrated transcriptomic data from patients and cellular models to identify a STAG2-dependent gene signature associated with worse prognosis. Subsequent genomic profiling and high-resolution chromatin interaction data from Capture Hi-C indicated that cohesin-STAG2 facilitates communication between EWS::FLI1-bound long GGAA repeats, presumably acting as neoenhancers, and their target promoters. Changes in CTCF-dependent chromatin contacts involving signature genes, unrelated to EWS::FLI1 binding, were also identified. STAG1 is unable to compensate for STAG2 loss an

SUBMITTER: Gimenez-Llorente D 

PROVIDER: S-EPMC11624272 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature