{
  "abstract": "Epithelial-mesenchymal transition (EMT) is an essential process in development, tissue repair, and tumour metastasis, and is triggered by SNAI, ZEB and TWIST transcription factors, that recruit lysine-specific demethylase 1 (LSD1) to repress epithelial genes such as E-cadherin. In mesenchymal cells, LSD1 inhibition restores E-cadherin expression and reduces migration and invasion, consistent with LSD1 inhibition reverting EMT, and offering a therapeutic modality for EMT-associated disease. Recent data, however, suggest context-dependent roles for LSD1, as its inhibition in epithelial cells increases mesenchymal marker expression, potentially promoting EMT. To investigate this discrepancy, we mapped genome-wide binding of LSD1 in HCT116 epithelial cells and used rapid degron-mediated ablation of endogenous LSD1 to measure changes in nascent and steady-state transcription and chromatin accessibility. In epithelial cells, LSD1 binds constitutively-accessible, primed mesenchymal promoters. These are rapidly derepressed after LSD1 ablation, with activation of SNAI2 and ZEB1, which repress epithelial hallmarks such as E-cadherin. Re-introduction of LSD1 downregulates SNAI2 and ZEB1 but, surprisingly, further represses E-cadherin, indicating sustained loss of epithelial characteristics. Collectively, our results show that LSD1 maintains epithelial identity by repressing mesenchymal genes, questioning the therapeutic utility of LSD1 inhibition for EMT control.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Structural and Chemical Biology and Division of Molecular and Cell Biology, University of Leicester, Leicester, LE1 7RH"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "R. E. Turnbull"
    },
    {
      "name": "O. Gonchar"
    },
    {
      "name": "K. Sirvydis"
    },
    {
      "name": "M. Iftikhar"
    },
    {
      "name": "M. E. Coulson"
    },
    {
      "name": "S. Y. Kwon"
    },
    {
      "name": "J. T. Hodgkinson"
    },
    {
      "name": "P. Badenhorst"
    },
    {
      "name": "S. M. Cowley"
    },
    {
      "affs": [
        0
      ],
      "name": "J. W. Schwabe"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0a59cx7e1cqbf.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.764245",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764245v1.full",
  "id": "0a59cx7e1cqbf",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764245v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764245v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0a59cx7e1cqbf.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:04Z",
      "native_id": "10.64898/2026.11.04.764245",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764245v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Global repression of mesenchymal genes in epithelial cells by the histone demethylase LSD1",
  "title_text": "Global repression of mesenchymal genes in epithelial cells by the histone demethylase LSD1",
  "type": "preprint",
  "updated_at": "2026-11-08T00:21:02Z",
  "url": "https://research.draconitic.com/paper/0a59cx7e1cqbf",
  "venue": "bioRxiv",
  "versions": []
}