{
  "abstract": "Essential roles for the PDX1 transcription factor in pancreatic development and β-cell function are well known, yet the structure-function relationships of domains within its C-terminus remain incompletely defined. We identified a focal intrinsically disordered region (IDR) spanning residues 207-223 of the PDX1 C-terminus and generated mice harboring deletion of this region (Pdx1Δ207). Despite normal protein levels, Pdx1Δ207 homozygous embryos exhibit severe pancreas hypoplasia by embryonic day (E)11.5, with particular impairment in endocrine differentiation. Although Pdx1Δ207 localization was predominantly nuclear in β cells, further biochemical analyses revealed loss of chromatin occupancy at PDX1 target genes and decreased transcriptional activation of the Ins2 promoter. Truncation of the C-terminus beginning at residue 211 had no effect on target gene occupancy, localizing the functional requirement to highly conserved residues 207-210. Interestingly, structural predictions suggest that residues 207-210 incorporate into an extended helical structure immediately adjacent to the PDX1 homeodomain, suggesting potential conformational transitions within this IDR. Taken together, these four conserved residues are required for optimal PDX1 chromatin occupancy and pancreas organogenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cell & Developmental Biology, Vanderbilt University, Nashville, TN 37240, USA",
    "Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA",
    "Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN 37232, USA",
    "Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232, USA",
    "Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA",
    "Department of Biological Sciences, Vanderbilt University, Nashville, TN 37240, USA",
    "Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA",
    "Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19105, USA",
    "Center for AI in Protein Dynamics, Vanderbilt University, Nashville, TN 37232, USA",
    "Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA",
    "Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA",
    "VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Anthony S. Wokasch"
    },
    {
      "affs": [
        1
      ],
      "name": "Muhammad Shamoon"
    },
    {
      "affs": [
        1
      ],
      "name": "Courtney Campbell"
    },
    {
      "affs": [
        2
      ],
      "name": "Tianqi Wu",
      "orcid": "0000-0002-1545-3462"
    },
    {
      "affs": [
        3
      ],
      "name": "Jennifer D. Fuhr"
    },
    {
      "affs": [
        4
      ],
      "name": "Anna Gilbert"
    },
    {
      "affs": [
        0
      ],
      "name": "Thomas Mehaffey",
      "orcid": "0009-0004-7526-0664"
    },
    {
      "affs": [
        5
      ],
      "name": "Carter M. Barnes"
    },
    {
      "affs": [
        6
      ],
      "name": "Neha Ahuja"
    },
    {
      "affs": [
        1
      ],
      "name": "Morgan A. Gingerich"
    },
    {
      "affs": [
        1
      ],
      "name": "Jie Zhu"
    },
    {
      "affs": [
        7
      ],
      "name": "Paul Gadue"
    },
    {
      "affs": [
        6
      ],
      "name": "Ondine Cleaver",
      "orcid": "0000-0003-2454-6641"
    },
    {
      "affs": [
        2,
        8
      ],
      "name": "Hassane Mchaourab",
      "orcid": "0000-0002-5673-0980"
    },
    {
      "affs": [
        9
      ],
      "name": "Doris A. Stoffers"
    },
    {
      "affs": [
        1,
        10,
        11
      ],
      "name": "Scott A. Soleimanpour"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Maureen Gannon",
      "orcid": "0000-0003-3287-8101"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ek8cay3k5fcww.bib",
  "cited_by": 0,
  "doi": "10.1242/dev.205842",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723409/",
  "id": "ek8cay3k5fcww",
  "issns": [
    "0950-1991",
    "1477-9129"
  ],
  "landing_url": "https://doi.org/10.1242/dev.205842",
  "language": "en",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2746|Pancreatic function and diabetes"
    ]
  ],
  "openalex": "W7213964869",
  "pdf_url": null,
  "pmcid": "PMC13723409",
  "pmid": "42768965",
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ek8cay3k5fcww.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:03Z",
      "native_id": "PMC13723409",
      "source": "pmc",
      "url": "https://doi.org/10.1242/dev.205842"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Pancreatic function and diabetes",
      "subfield": "surgery"
    }
  ],
  "title": "Conserved C-terminal residues adjacent to the canonical PDX1 homeodomain are required for chromatin occupancy and pancreas development",
  "title_text": "Conserved C-terminal residues adjacent to the canonical PDX1 homeodomain are required for chromatin occupancy and pancreas development",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:14Z",
  "url": "https://research.draconitic.com/paper/ek8cay3k5fcww",
  "venue": "Development (Cambridge, England)",
  "versions": []
}