{
  "abstract": "Cys2-His2-zinc-finger proteins (C2H2-ZFPs) form the largest class of human transcription factors, yet their potential roles in higher-order genome organization remain poorly defined. To date, only a few C2H2-ZFPs, e.g. CTCF, have been implicated in chromatin organization. Here, we systematically examined the global relationship between C2H2-ZFPs and long-range chromatin interactions (LRIs). By integrating ChIP-seq datasets for 216 C2H2-ZFPs with genome-wide chromatin interaction maps, we find that &gt;40% of human C2H2-ZFPs are significantly enriched at LRI anchors. Depletion of a subset of such C2H2-ZFPs is associated with altered expression of genes linked by the LRIs they occupy. To investigate whether protein–protein interactions (PPIs) contribute to this pattern, we generated a large-scale interactome using affinity purification-mass spectrometry, encompassing 345 C2H2-ZFPs, and LUMIER binary interaction assays for 204 C2H2-ZFPs, revealing extensive connectivity among the family members. Integrative analysis of PPIs, ChIP-seq, and chromatin interaction datasets revealed that interacting C2H2-ZFP pairs are significantly co-enriched at LRIs and frequently localize to the same or opposing loop anchors. Finally, we show that ∼35% of LRI-associated C2H2-ZFP binding sites overlap somatic mutations in cancer genomes. Together, our results reveal a widespread network of C2H2-ZFP interactions at chromatin loop anchors, providing an important resource for understanding chromatin organization.",
  "abstract_shown": true,
  "affiliations": [
    "Donnelly Centre, University of Toronto , Toronto, ON M5S 3E1 ,",
    "Department of Molecular Genetics, University of Toronto , Toronto, ON M5S 1A8 ,",
    "Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto , Toronto, ON M5S 1A8 ,",
    "Department of Computer Science, Stanford University , Stanford, CA 94305 ,",
    "Ray and Stephanie Lane Department of Computational Biology, Carnegie Mellon University , Pittsburgh, PA 15213 ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ernest Radovani"
    },
    {
      "affs": [
        0
      ],
      "name": "Syed Nabeel-Shah",
      "orcid": "0000-0002-4239-7443"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Edyta Marcon"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuye Pu"
    },
    {
      "affs": [
        0
      ],
      "name": "Guoqing Zhong"
    },
    {
      "affs": [
        0
      ],
      "name": "Hua Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongbo Guo"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Irene M Kaplow",
      "orcid": "0000-0002-8924-8269"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Andrew Emili",
      "orcid": "0000-0001-8995-246X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Timothy R Hughes",
      "orcid": "0000-0002-8721-4719"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jack F Greenblatt",
      "orcid": "0000-0003-1762-2861"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/46w8pxg1dns34.bib",
  "cited_by": 1,
  "doi": "10.1093/nar/gkag1004",
  "fulltext_url": "https://europepmc.org/articles/PMC13678222",
  "id": "46w8pxg1dns34",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1004/8937191",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7134247817",
  "pdf_url": "https://academic.oup.com/nar/article-pdf/54/19/gkag1004/72085475/gkag1004.pdf",
  "pmcid": "PMC13678222",
  "pmid": "42895067",
  "published": "2026-10-01",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/46w8pxg1dns34.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:50Z",
      "native_id": "10.1093/nar/gkag1004",
      "source": "crossref",
      "url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1004/8937191"
    },
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42895067",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42895067"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Integrative analysis reveals extensive interactions among C2H2 zinc finger proteins at chromatin loop anchors",
  "title_text": "Integrative analysis reveals extensive interactions among C2H2 zinc finger proteins at chromatin loop anchors",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/46w8pxg1dns34",
  "venue": "Nucleic Acids Research",
  "versions": []
}