{
  "abstract": "In eukaryotes, transcription factors (TFs) must continuously compete with nucleosomes to access their binding sites, leading to cell-to-cell variability in chromatin accessibility at regulatory regions. Although critical to understand enhancer function in transcription, the mechanisms that define how frequently an enhancer is active in a cell population remain unclear. Here we used single-molecule footprinting to quantify the frequency at which chromatin is accessible at enhancers in response to TF perturbations and changes in their chromatin environment. We find that, individually, most TFs open chromatin in a small fraction of cells, and that cumulative TF binding controls enhancer activation frequency. Moreover, testing the functionality of hundreds of enhancers when inserted at an ectopic genomic location indicates that p300 activity is required for their full activation. Our data support a model in which enhancer activation frequency depends on the cumulative function of multiple TFs and is modulated by p300 activity.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Biosciences, Collaboration for Joint PhD Degree between EMBL and Heidelberg University, Heidelberg, Germany",
    "Genome Biology Unit, EMBL Heidelberg, Heidelberg, Germany",
    "Institut Imagine, Paris, France",
    "Division of Precision Medicine, NYU Grossman School of Medicine, New York City, NY, USA",
    "Division of Medical Bioinformatics, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand",
    "German Cancer Research Center (DKFZ), Division of Regulatory Genomics and Cancer Evolution, Heidelberg, Germany",
    "Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium",
    "VIB Center for Inflammation Research, Ghent, Belgium",
    "Department of Biomedicine, University of Basel, Basel, Switzerland. judith.zaugg@embl.de",
    "Structural and Computational Biology Unit, EMBL Heidelberg, Heidelberg, Germany. judith.zaugg@embl.de",
    "Genome Biology Unit, EMBL Heidelberg, Heidelberg, Germany. arnaud.krebs@embl.de"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Valentina Baderna",
      "orcid": "0000-0002-2053-3926"
    },
    {
      "affs": [
        3,
        0,
        1
      ],
      "name": "Guido Barzaghi",
      "orcid": "0000-0001-6066-3920"
    },
    {
      "affs": [
        1
      ],
      "name": "Rozemarijn Kleinendorst",
      "orcid": "0000-0003-1803-8982"
    },
    {
      "affs": [
        4,
        1
      ],
      "name": "Kasit Chatsirisupachai",
      "orcid": "0000-0001-9446-6714"
    },
    {
      "affs": [
        1
      ],
      "name": "Laura Moniot-Perron",
      "orcid": "0000-0002-6224-6925"
    },
    {
      "affs": [
        1
      ],
      "name": "Colm Doyle"
    },
    {
      "affs": [
        5
      ],
      "name": "Meike Schopp"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Tino Hochepied",
      "orcid": "0000-0001-5897-2054"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Claude Libert",
      "orcid": "0000-0001-6408-036X"
    },
    {
      "affs": [
        5
      ],
      "name": "Duncan T. Odom",
      "orcid": "0000-0001-6201-5599"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Judith B. Zaugg",
      "orcid": "0000-0001-8324-4040"
    },
    {
      "affs": [
        10
      ],
      "name": "Arnaud Regis Krebs",
      "orcid": "0000-0001-7999-6127"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5kh1s600rtap3.bib",
  "cited_by": 9,
  "doi": "10.1038/s41588-026-02703-x",
  "fulltext_url": null,
  "id": "5kh1s600rtap3",
  "issns": [
    "1061-4036",
    "1546-1718"
  ],
  "landing_url": "https://doi.org/10.1038/s41588-026-02703-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7171940685",
  "pdf_url": "https://www.nature.com/articles/s41588-026-02703-x.pdf",
  "pmcid": "PMC13447113",
  "pmid": "42538372",
  "published": "2026-07-31",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/5kh1s600rtap3.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T13:20:49Z",
      "native_id": "W7171940685",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41588-026-02703-x"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Cumulative transcription factor binding and p300-mediated histone acetylation drive enhancer activation frequency",
  "title_text": "Cumulative transcription factor binding and p300-mediated histone acetylation drive enhancer activation frequency",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T13:20:49Z",
  "url": "https://research.draconitic.com/paper/5kh1s600rtap3",
  "venue": "Nature Genetics",
  "versions": []
}