{
  "abstract": "Ewing sarcoma is an aggressive bone malignancy occurring in children, adolescents, and young adults. Most cases are caused by expression of the fusion oncoprotein EWSR1::FLI1, which contains the low complexity domain (LCD) of EWSR1 and the DNA-binding domain (DBD) of FLI1. Previous genomic studies indicate EWSR1::FLI1 accesses GGAA microsatellites in chromatin to function as a potent transcriptional regulator. Due to the technical challenges of purifying full-length EWSR1::FLI1, mechanistic studies biochemically characterizing its pioneer activities have been lacking. Here, we purified both full-length EWSR1::FLI1 and truncated DBD constructs to conduct biochemical and fluorescence-based experiments investigating interactions with different motifs in free DNA and nucleosomes. Both truncated and full-length EWSR1::FLI1 show efficient target binding in nucleosomes, and that the fourth alpha-helix in the FLI1 DBD enhances nucleosome-binding efficiency. Surprisingly, we also observe differences in both free DNA binding affinity and sequence preference between truncated and full-length proteins, though these changes are not apparent in nucleosome-binding assays. These findings reveal that EWSR1::FLI1 possesses a key pioneer factor property, efficiently targeting its binding site within nucleosomes, and that full-length EWSR1::FLI1 binding shifts to preferentially target GGAA repeats, even on motifs that bind a single EWSR1::FLI1 protein.",
  "abstract_shown": true,
  "affiliations": [
    "Nationwide Children's Hospital"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "R.-W. Chen"
    },
    {
      "name": "R. Zhou"
    },
    {
      "name": "E. J. Tokarsky"
    },
    {
      "name": "M. A. Boone"
    },
    {
      "name": "A. K. Byrum"
    },
    {
      "name": "M. G. Poirier"
    },
    {
      "affs": [
        0
      ],
      "name": "E. R. Theisen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/557pnkbn9d7q0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.752125",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752125v1.full",
  "id": "557pnkbn9d7q0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752125v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7213534934",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752125v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/557pnkbn9d7q0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:00Z",
      "native_id": "10.64898/2026.09.16.752125",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752125v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Fusion Oncoprotein EWSR1::FLI1 Invades Nucleosomes at Consensus ETS Motifs and GGAA Microsatellites",
  "title_text": "Fusion Oncoprotein EWSR1::FLI1 Invades Nucleosomes at Consensus ETS Motifs and GGAA Microsatellites",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:00Z",
  "url": "https://research.draconitic.com/paper/557pnkbn9d7q0",
  "venue": "bioRxiv",
  "versions": []
}