ArticleNucleic acids research2022
EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 51 citations in OpenAlex.
- Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- A Practical Compass to Biological Digital Resources and Omics Integration in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Article
- LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma.Cancer research communications · 2026Article
- Genome-wide association study meta-analysis identifies susceptibility loci informing Ewing sarcoma etiology and potential mechanisms of risk.medRxiv : the preprint server for health sciences · 2026Article
- New cell lines expanding the diversity of Ewing sarcoma models.International journal of cancer · 2026Article
- Epigenetic Regulation of Higher-Order Chromatin Structure (HOCS) and Its Implication in Human Diseases.Cancers · 2026Review
- Article
- Deregulated enhancer-promoter communication in cancer through altered nuclear architecture.International journal of cancer · 2026Review
- Precision oncology in the treatment of patients with bone sarcomas: an up-to-date narrative review.Exploration of targeted anti-tumor therapy · 2026Review
- The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.NPJ precision oncology · 2025Article
- LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Targeting developmental vulnerabilities in childhood sarcomas.Cancer metastasis reviews · 2025Review
- Seclidemstat (SP-2577) Induces Transcriptomic Reprogramming and Cytotoxicity in Multiple Fusion-Positive Sarcomas.Cancer research communications · 2025Article
- Subversion of mRNA degradation pathways by EWSR1::FLI1 represents a therapeutic vulnerability in Ewing sarcoma.Nature communications · 2025Article
- Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.Molecular oncology · 2025Article
- Liquid condensates: a new barrier to loop extrusion?Cellular and molecular life sciences : CMLS · 2025Review
- Integrative analysis of Ewing's sarcoma reveals that the MIF-CD74 axis is a target for immunotherapy.Cell communication and signaling : CCS · 2025Article
- Convergent pairs of highly transcribed genes restrict chromatin looping in Dictyostelium discoideum.Nucleic acids research · 2025Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Ewing sarcoma is a prototypical fusion transcription factor-associated pediatric cancer that expresses EWS/FLI or a highly related FET/ETS chimera. EWS/FLI dysregulates transcription to induce and maintain sarcomagenesis, but the mechanisms utilized are not fully understood. We therefore sought to define the global effects of EWS/FLI on chromatin conformation and transcription in Ewing sarcoma cells using a well-validated 'knock-down/rescue' model of EWS/FLI function in combination with next generation sequencing assays to evaluate how the chromatin landscape changes with loss, and recovery, of EWS/FLI expression. We found that EWS/FLI (and EWS/ERG) genomic localization is largely conserved across multiple patient-derived Ewing sarcoma cell lines. This EWS/FLI binding signature is associated with establishment of topologically-associated domain (TAD) boundaries, compartment activation, enhancer-promoter looping that involve both intra- and inter-TAD interactions, and gene activation. In addition, EWS/FLI co-localizes with the loop-extrusion factor cohesin to promote chromatin loops and TAD boundaries. Importantly, local chromatin features provide the basis for transcriptional heterogeneity in regulation of direct EWS/FLI target genes across different Ewing sarcoma cell lines. These data demonstrate a key role of EWS/FLI in mediating genome-wide changes in chromatin configuration and support the notion that fusion transcription factors serve as master regulators of three-dimensional reprogramming of chromatin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.