KDM6 Demethylases Contribute to EWSR1::FLI1-Driven Oncogenic Reprogramming in Ewing Sarcoma.

ABSTRACT: Ewing sarcoma is a highly aggressive tumor arising in bones and soft tissues, driven by the fusion oncoprotein EWSR1::FLI1. This aberrant transcription factor binds to GGAA microsatellites, causing epigenetic reprogramming through the formation of active neoenhancers in a permissive cellular context. Inhibition of the oncogene remains challenging, and current efforts seek to exploit emergent epigenetic treatments targeting EWSR1::FLI1 cofactors. In Ewing sarcoma, neoenhancers are characterized by strong enrichment of the active H3K27ac mark and a concomitant lack of the repressive H3K27me3 mark. These regions are typically decorated with high levels of H3K27me3 prior to EWSR1::FLI1 activation. In this study, upon expression of EWSR1::FLI1 in human pediatric mesenchymal stem cells, consider

SUBMITTER: Figuerola-Bou E 

PROVIDER: S-EPMC12616242 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature