{
  "abstract": "Cohesin plays a central role in three-dimensional genome organization and transcriptional regulation, with functional diversity determined by incorporation of distinct STAG subunits. Pathogenic variants in the X-linked STAG2 gene cause a rare cohesinopathy with variable clinical manifestations. Molecular analyses of fibroblasts from females carrying germline STAG2-truncating variants revealed highly skewed X chromosome inactivation favoring the mutant allele, resulting in loss of STAG2 expression in most cases. STAG2-deficient cells displayed a proliferative advantage and transcriptional alterations without detectable defects in sister chromatid cohesion or DNA repair. Notably, compensatory upregulation of STAG1 and ectopic expression of the germ cell-specific paralog STAG3 were observed, leading to the formation of a previously unrecognized chimeric cohesin complex in somatic cells. These findings suggest that females with STAG2-truncating variants exhibit mosaicism for STAG2 expression and compensatory STAG3 incorporation, providing mechanistic insight into the phenotypic variability observed in STAG2-associated cohesinopathies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Macarena Moronta Gines"
    },
    {
      "name": "Marja W. Wessels"
    },
    {
      "name": "Valentina Casa"
    },
    {
      "name": "Thomas van Staveren"
    },
    {
      "name": "Amber Hof"
    },
    {
      "name": "Wendy K. Chung"
    },
    {
      "name": "Marjolaine Willems"
    },
    {
      "name": "Anna Sandestig"
    },
    {
      "name": "Irina Huening"
    },
    {
      "name": "Peter Turnpenny"
    },
    {
      "name": "Mathilde Lefebvre"
    },
    {
      "name": "Ilaria Parenti"
    },
    {
      "name": "Frank J. Kaiser"
    },
    {
      "name": "Jeroen Demmers"
    },
    {
      "name": "Wilfred F.J. van Ijcken"
    },
    {
      "name": "Kerstin S. Wendt"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5xmngmbhx56jr.bib",
  "cited_by": 2,
  "doi": "10.1016/j.isci.2025.114195",
  "fulltext_url": null,
  "id": "5xmngmbhx56jr",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://hal.science/hal-05738655v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.gen"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "openalex",
      "1312|Chromatin Remodeling and Cancer"
    ]
  ],
  "openalex": "W4416549014",
  "pdf_url": "https://hal.science/hal-05738655/document",
  "pmcid": null,
  "pmid": "41492387",
  "published": "2026-09-04",
  "publisher": "Cell Press, Elsevier [2018-....]",
  "ris": "https://research.draconitic.com/paper/5xmngmbhx56jr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:29Z",
      "native_id": "hal-05738655",
      "source": "hal",
      "url": "https://hal.science/hal-05738655v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.gen",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.mhep",
      "subfield": "general"
    }
  ],
  "title": "STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling",
  "title_text": "STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:29Z",
  "url": "https://research.draconitic.com/paper/5xmngmbhx56jr",
  "venue": "iScience",
  "versions": []
}