{
  "abstract": "There is ongoing debate regarding the degree to which transcription factors (TFs) independently specify genomic binding: TF binding motifs are typically short and degenerate, yielding many more binding site predictions than observed in cells. Here we present genomic high-throughput SELEX (GHT-SELEX)—a scalable method that surveys intrinsic binding of purified TFs to the fragmented, naked and unmodified genome. GHT-SELEX peaks for 179 diverse human TFs display surprisingly high overlap with chromatin immunoprecipitation sequencing peaks for the same TF. Comparable overlap can be obtained from motifs using appropriate analytical approaches. For C2H2 zinc finger (zf) proteins—the largest class of human TFs—GHT-SELEX shows that modular, alternative engagement of C2H2-zf domains is the norm, enabling several types of distinct target sites, and frequently involving internal duplication and divergence within the C2H2-zf array. Altogether, it is common for TFs to delineate a large fraction of in vivo genomic binding sites independently of other cellular factors.",
  "abstract_shown": true,
  "affiliations": [
    "Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. arttu.jolma@utoronto.ca",
    "Donnelly Centre, University of Toronto, Toronto, ON M5S 3E, Canada",
    "Department of Human Genetics, McGill University, Montreal, Quebec, Canada",
    "Victor P. Dahdaleh Institute of Genomic Medicine, Montreal, Quebec, Canada",
    "Department of Human Genetics, McGill University, Montréal, QC H3A 0C7, Canada",
    "Victor P. Dahdaleh Institute of Genomic Medicine, Montréal, QC HA 0G1, Canada",
    "Donnelly Centre, University of Toronto, Toronto, Ontario, Canada",
    "Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada",
    "Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada",
    "Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA",
    "Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 1006, USA",
    "Swiss Institute of Bioinformatics, Lausanne, Switzerland",
    "Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia",
    "Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia and Institute of Protein Research, Russian Academy of Sciences, 142290, Pushchino, Russia",
    "Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland",
    "Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada",
    "Institute of Computer Science, Martin Luther University Halle-Wittenberg, Halle, Germany",
    "Bioinformatics Laboratory, Federal Research Center for Information and Computational Technologies, Novosibirsk, Russia",
    "Department of Computational Biology, Sirius University of Science and Technology, Sirius, Russia",
    "Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia",
    "Institute of Protein Research, Russian Academy of Sciences, Pushchino, Russia",
    "Bioinformatics Competence Center, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland",
    "Bioinformatics Competence Center, Université de Lausanne, Lausanne, Switzerland",
    "Chugai Pharmaceutical Co. Ltd, Tokyo, Japan",
    "Biosoft.Ru LLC, Novosibirsk, Russia",
    "Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia",
    "Computer Science Institute, Faculty of Mathematics and Physics, Charles University, Prague, Czech Republic",
    "Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic",
    "Max Planck Institute of Biochemistry, Planegg, Germany",
    "Altius Institute for Biomedical Sciences, Seattle, WA, USA",
    "Center for Molecular and Cellular Bioengineering (CMCB), TUD Dresden University of Technology, Biotechnologisches Zentrum (BIOTEC), Dresden, Germany",
    "Cincinnati Children’s Hospital, Cincinnati, OH, USA",
    "Institute of Biochemistry and Genetics, Ufa Federal Research Centre of Russian Academy of Sciences, Ufa, Russia",
    "Department of Human Genetics, McGill University, Montreal, Quebec, Canada. hamed.najafabadi@mcgill.ca",
    "Victor P. Dahdaleh Institute of Genomic Medicine, Montreal, Quebec, Canada. hamed.najafabadi@mcgill.ca",
    "Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. t.hughes@utoronto.ca",
    "Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. t.hughes@utoronto.ca"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 51,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Arttu Jolma",
      "orcid": "0000-0002-2543-7490"
    },
    {
      "affs": [
        2,
        3,
        4,
        5
      ],
      "name": "Aldo Hernández-Corchado",
      "orcid": "0000-0003-0682-3959"
    },
    {
      "affs": [
        6,
        1
      ],
      "name": "Ally W. H. Yang",
      "orcid": "0000-0002-8678-0946"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Ali Fathi",
      "orcid": "0009-0007-1441-9653"
    },
    {
      "affs": [
        9,
        6,
        1,
        10
      ],
      "name": "Kaitlin U. Laverty",
      "orcid": "0009-0004-4341-4665"
    },
    {
      "affs": [
        6,
        1
      ],
      "name": "Alexander V. Brechalov",
      "orcid": "0000-0003-0540-4517"
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    {
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        6,
        1
      ],
      "name": "Rozita Razavi",
      "orcid": "0009-0000-5466-6519"
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    {
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        6,
        1
      ],
      "name": "Mihai Albu",
      "orcid": "0009-0000-8417-681X"
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    {
      "affs": [
        6,
        1
      ],
      "name": "Hong Zheng",
      "orcid": "0009-0004-1981-110X"
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      "affs": [
        11,
        12,
        13
      ],
      "name": "Philipp Bücher",
      "orcid": "0000-0003-4824-885X"
    },
    {
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        14,
        11,
        4,
        5
      ],
      "name": "Bart Deplancke",
      "orcid": "0000-0001-9935-843X"
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    {
      "affs": [
        15,
        8,
        1
      ],
      "name": "Oriol Fornés",
      "orcid": "0000-0002-5969-3054"
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    {
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        16
      ],
      "name": "Jan Grau",
      "orcid": "0000-0003-2081-6405"
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    {
      "affs": [
        16
      ],
      "name": "Ivo Große",
      "orcid": "0000-0001-5318-4825"
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    {
      "affs": [
        17,
        18
      ],
      "name": "Fedor A. Kolpakov"
    },
    {
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        19
      ],
      "name": "Vsevolod J. Makeev",
      "orcid": "0000-0001-9405-9748"
    },
    {
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        6
      ],
      "name": "Marjan Barazandeh",
      "orcid": "0000-0003-3420-3669"
    },
    {
      "affs": [
        6
      ],
      "name": "Zhenfeng Deng",
      "orcid": "0009-0006-3881-9312"
    },
    {
      "affs": [
        6
      ],
      "name": "Chun Hu"
    },
    {
      "affs": [
        6
      ],
      "name": "Samuel A. Lambert",
      "orcid": "0000-0001-8222-008X"
    },
    {
      "affs": [
        6
      ],
      "name": "Zain M. Patel"
    },
    {
      "affs": [
        6
      ],
      "name": "Sara E. Pour",
      "orcid": "0009-0009-6201-1921"
    },
    {
      "affs": [
        6
      ],
      "name": "Mikhail Salnikov"
    },
    {
      "affs": [
        6
      ],
      "name": "Isaac Yellan",
      "orcid": "0000-0001-6622-1189"
    },
    {
      "affs": [
        20
      ],
      "name": "Georgy Meshcheryakov"
    },
    {
      "affs": [
        21,
        22
      ],
      "name": "Giovanna Ambrosini",
      "orcid": "0000-0003-1294-6541"
    },
    {
      "affs": [
        14,
        11
      ],
      "name": "Antoni J. Gralak",
      "orcid": "0009-0007-1086-6165"
    },
    {
      "affs": [
        23
      ],
      "name": "Sachi Inukai",
      "orcid": "0000-0002-6404-1384"
    },
    {
      "affs": [
        14,
        11
      ],
      "name": "Judith F. Kribelbauer-Swietek",
      "orcid": "0000-0002-8072-7773"
    },
    {
      "affs": [
        16
      ],
      "name": "Marie-Luise Plescher",
      "orcid": "0009-0006-6163-9782"
    },
    {
      "affs": [
        18
      ],
      "name": "Semyon K. Kolmykov",
      "orcid": "0000-0002-9259-0495"
    },
    {
      "affs": [
        24
      ],
      "name": "Ivan Yevshin"
    },
    {
      "affs": [
        20
      ],
      "name": "Nikita Gryzunov",
      "orcid": "0009-0000-0782-8650"
    },
    {
      "affs": [
        25,
        20,
        19
      ],
      "name": "Ivan Kozin",
      "orcid": "0009-0009-4603-8550"
    },
    {
      "affs": [
        25
      ],
      "name": "Mikhail Nikonov"
    },
    {
      "affs": [
        25
      ],
      "name": "Vladimir Nozdrin",
      "orcid": "0009-0004-3053-1387"
    },
    {
      "affs": [
        25
      ],
      "name": "Arsenii O. Zinkevich",
      "orcid": "0000-0001-9450-4629"
    },
    {
      "affs": [
        26,
        27
      ],
      "name": "Kateřina Faltejsková",
      "orcid": "0000-0001-7390-8077"
    },
    {
      "affs": [
        28
      ],
      "name": "Pavel Kravchenko",
      "orcid": "0000-0002-5751-7129"
    },
    {
      "affs": [
        29,
        19
      ],
      "name": "Sergey Abramov",
      "orcid": "0000-0002-3334-5334"
    },
    {
      "affs": [
        29,
        19
      ],
      "name": "Alexandr Boytsov",
      "orcid": "0000-0002-2712-8368"
    },
    {
      "affs": [
        19
      ],
      "name": "Vasilii Kamenets"
    },
    {
      "affs": [
        19
      ],
      "name": "Dmitry Penzar"
    },
    {
      "affs": [
        30
      ],
      "name": "Anton Vlasov",
      "orcid": "0000-0001-8558-9763"
    },
    {
      "affs": [
        19
      ],
      "name": "Ilya E. Vorontsov",
      "orcid": "0000-0001-8888-0804"
    },
    {
      "affs": [
        9
      ],
      "name": "Quaid Morris"
    },
    {
      "affs": [
        31
      ],
      "name": "Xiaoting Chen",
      "orcid": "0000-0002-3782-3962"
    },
    {
      "affs": [
        31
      ],
      "name": "Matthew T. Weirauch",
      "orcid": "0000-0001-7977-9122"
    },
    {
      "affs": [
        32,
        20,
        19
      ],
      "name": "Ivan V. Kulakovskiy",
      "orcid": "0000-0002-6554-8128"
    },
    {
      "affs": [
        33,
        34
      ],
      "name": "Hamed Shateri Najafabadi",
      "orcid": "0000-0003-2735-4231"
    },
    {
      "affs": [
        35,
        36
      ],
      "name": "Timothy Hughes",
      "orcid": "0000-0002-8022-6012"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a61j3bfpj8e6j.bib",
  "cited_by": 13,
  "doi": "10.1038/s41592-026-03177-9",
  "fulltext_url": null,
  "id": "a61j3bfpj8e6j",
  "issns": [
    "1548-7091",
    "1548-7105"
  ],
  "landing_url": "https://doi.org/10.1038/s41592-026-03177-9",
  "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"
    ]
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  "openalex": "W4404259719",
  "pdf_url": "https://www.nature.com/articles/s41592-026-03177-9.pdf",
  "pmcid": "PMC11601218",
  "pmid": "39605368",
  "published": "2026-08-05",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/a61j3bfpj8e6j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W4404259719",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41592-026-03177-9"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors",
  "title_text": "GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:43Z",
  "url": "https://research.draconitic.com/paper/a61j3bfpj8e6j",
  "venue": "Nature Methods",
  "versions": []
}