{
  "abstract": "Three-dimensional genome organization is crucial for gene regulation and cell identity. The architectural proteins CTCF and the cohesin complex mediate chromatin looping, shaping cell-type-specific transcription. While their functions have been extensively characterized in embryonic stem cells and other proliferative systems, the regulation of transcription by these two ubiquitously expressed factors in terminally differentiated cells, such as endothelial cells (ECs), remains poorly understood. Moreover, interpretation of prior studies is further complicated by the essential requirement of CTCF and cohesin for cell viability, as most rely on near-complete depletion. Consequently, the extent to which CTCF and cohesin function redundantly, cooperatively, or independently to regulate cell-type-specific programs in differentiated cells remains a major knowledge gap. To address this, we reduced CTCF or the core cohesin subunit RAD21 to approximately 50% protein levels in an isogenic system of human induced pluripotent stem cells (iPSCs) and iPSC-derived endothelial cells (iEcs), enabling direct comparison between undifferentiated and lineage-committed cell states. CUT&Tag and RNA sequencing revealed a striking, EC-specific loss of CTCF and RAD21 occupancy at gene promoters following partial depletion; RAD21 reduction had a more pronounced impact on endothelial gene expression than CTCF depletion. RAD21 loss also led to a marked redistribution of FLI1 binding, a transcription factor essential for endothelial identity and function. Collectively, our findings highlight critical contributions of RAD21 in EC-specific gene expression through coordinated control of chromatin architecture and modulating transcription factor occupancy, providing mechanistic insight into cohesin-dependent regulation of vascular transcriptional programs.",
  "abstract_shown": true,
  "affiliations": [
    "Versiti Blood Research Institute, Milwaukee, WI, USA",
    "Department of Physiology, University of Arizona, Tucson, AZ, USA",
    "Amrita School of Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Ernakulam, India",
    "Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA",
    "Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA",
    "Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI, USA",
    "Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA",
    "Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA",
    "Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA",
    "The Jackson Laboratory, Bar Harbor, ME, USA",
    "Department of Pediatrics, Section of Hematology/Oncology/Transplantation, Medical College of Wisconsin, Milwaukee, WI, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Atrayee Ray",
      "orcid": "0000-0002-6731-4317"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Rajan Pandey"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniel Bennett Chrisenberry"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Josiah D. Murray"
    },
    {
      "affs": [
        0
      ],
      "name": "Cary Stelloh"
    },
    {
      "affs": [
        1
      ],
      "name": "Pengyuan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yong Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Qiongzi Qiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Alison E. Meyer"
    },
    {
      "affs": [
        4
      ],
      "name": "Monika Tutaj"
    },
    {
      "affs": [
        5
      ],
      "name": "Chien-Wei Lin"
    },
    {
      "affs": [
        6
      ],
      "name": "Khanmi Kasomva"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael Sadowski"
    },
    {
      "affs": [
        5,
        7
      ],
      "name": "Paul Auer"
    },
    {
      "affs": [
        8
      ],
      "name": "Michael E. Widlansky"
    },
    {
      "affs": [
        4
      ],
      "name": "Aron M. Geurts"
    },
    {
      "affs": [
        4
      ],
      "name": "Allen W. Cowley"
    },
    {
      "affs": [
        4
      ],
      "name": "Anne E. Kwitek"
    },
    {
      "affs": [
        9
      ],
      "name": "Andrew S. Greene"
    },
    {
      "affs": [
        1
      ],
      "name": "Mingyu Liang"
    },
    {
      "affs": [
        0,
        3,
        10
      ],
      "name": "Sridhar Rao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aes9nvnsgdat2.bib",
  "cited_by": 0,
  "doi": "10.1080/15592294.2026.2749250",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13699836/",
  "id": "aes9nvnsgdat2",
  "issns": [
    "1559-2294",
    "1559-2308"
  ],
  "landing_url": "https://doi.org/10.1080/15592294.2026.2749250",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "lcc",
      "QH426-470"
    ],
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      "openalex",
      "1312|Genomics and Chromatin Dynamics"
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  "pdf_url": "https://europepmc.org/articles/PMC13699836?pdf=render",
  "pmcid": "PMC13699836",
  "pmid": "42925159",
  "published": "2026-10-23",
  "publisher": "Taylor & Francis",
  "ris": "https://research.draconitic.com/paper/aes9nvnsgdat2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:23Z",
      "native_id": "PMC13699836",
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      "first_seen": "2026-10-30T13:44:05Z",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Chromatin rewiring in endothelial cells upon cohesin reduction redistributes genome-wide FLI1 binding",
  "title_text": "Chromatin rewiring in endothelial cells upon cohesin reduction redistributes genome-wide FLI1 binding",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:05Z",
  "url": "https://research.draconitic.com/paper/aes9nvnsgdat2",
  "venue": "Epigenetics",
  "versions": []
}