Highly connected 3D chromatin networks established by an oncogenic fusion protein shape tumor cell identity.

ABSTRACT: Cell fate transitions observed in embryonic development involve changes in three-dimensional genomic organization that provide proper lineage specification. Whether similar events occur within tumor cells and contribute to cancer evolution remains largely unexplored. We modeled this process in the pediatric cancer Ewing sarcoma and investigated high-resolution looping and large-scale nuclear conformation changes associated with the oncogenic fusion protein EWS-FLI1. We show that chromatin interactions in tumor cells are dominated by highly connected looping hubs centered on EWS-FLI1 binding sites, which directly control the activity of linked enhancers and promoters to establish oncogenic expression programs. Conversely, EWS-FLI1 depletion led to the disassembly of these looping networks a

SUBMITTER: Sanalkumar R 

PROVIDER: S-EPMC10718307 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature