{
  "abstract": "The Kaposi's sarcoma-associated herpesvirus oncoprotein vIRF3 is essential for primary effusion lymphoma (PEL) cell survival and cooperates with cellular interferon regulatory factor 4 (IRF4) to activate super-enhancers (SEs) controlling MYC and IRF4. However, the DNA sequence requirements for this cooperation are unknown. Using reporter assays, we mapped vIRF3/IRF4 responsiveness within the IRF4-SE to an ∼83-bp element activated by vIRF3 alone and cooperatively by vIRF3 and IRF4. vIRF3-dependent activation required an AP-1 motif, whereas cooperation with IRF4 required IRF4 DNA binding and IRF-related motifs outside canonical AP-1-IRF composite elements (AICEs). These motifs were necessary but insufficient outside their native sequence context, indicating a requirement for extended flanking sequences. DNA pulldowns revealed distinct motif requirements for vIRF3 and IRF4 association with the IRF4-SE. A distal MYC-SE required a similarly extended region containing a functional AICE2 motif, with vIRF3 activity depending primarily on its AP-1 half-site. Motif requirements were preserved in integrated reporter assays. BATF promoted vIRF3/IRF4-dependent activation preferentially in integrated reporters and was required to maintain vIRF3 and IRF4 occupancy at the endogenous MYC-SE. These findings define context-dependent DNA and cofactor requirements through which vIRF3 co-opts IRF4-regulated oncogenic enhancers in PEL.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States.",
    "Departments of Biochemistry and Molecular Genetics and Preventive Medicine (Biostatistics and Informatics), Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ziyan Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Christine B Magdongon"
    },
    {
      "affs": [
        0
      ],
      "name": "Haocong Katherine Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Maureen E Haynes"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingyi Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Elizabeth T Bartom"
    },
    {
      "affs": [
        0
      ],
      "name": "Eva Gottwein",
      "orcid": "0000-0002-4519-2259"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7z3crx0g7f5xc.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag942",
  "fulltext_url": "https://europepmc.org/articles/PMC13635746",
  "id": "7z3crx0g7f5xc",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://europepmc.org/article/MED/42831422",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W4413141542",
  "pdf_url": "https://europepmc.org/articles/PMC13635746?pdf=render",
  "pmcid": "PMC13635746",
  "pmid": "42831422",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7z3crx0g7f5xc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42831422",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42831422"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "KSHV-encoded vIRF3 cooperates with cellular IRF4 to drive super-enhancer activity through complex DNA elements.",
  "title_text": "KSHV-encoded vIRF3 cooperates with cellular IRF4 to drive super-enhancer activity through complex DNA elements.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/7z3crx0g7f5xc",
  "venue": "Nucleic acids research",
  "versions": []
}