2026-05-17T01:15:43Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/254372025-12-18T12:56:18Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991
Repisalud
author
Giménez-Llorente, Daniel
author
Cuadrado, Ana
author
Andreu, María José
author
Sanclemente-Alamán, Inmaculada
author
Solé-Ferran, Maria
author
Rodríguez-Corsino, Miriam
author
Losada, Ana
funder
Asociación Española Contra el Cáncer
funder
Comunidad de Madrid (España)
2024-11-06T06:34:12Z
2024-11-06T06:34:12Z
2024-11-01
EMBO Rep . 2024 Nov 1.
EMBO Reports
39487368
https://hdl.handle.net/20.500.12105/25437
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 and chromatin-bound cohesin is severely decreased, while levels of the processivity factor NIPBL remain unchanged, likely affecting DNA looping dynamics. These results illuminate how STAG2 loss modifies the chromatin interactome of Ewing sarcoma cells and provide a list of potential biomarkers and therapeutic targets.
eng
Cohesin
Genome Organization
Pediatric Cancer
Transcription
STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.
research article
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