{
  "abstract": "Housekeeping genes maintain robust expression across cell types despite dynamic transcription factor fluctuations, yet their haploinsufficiency is associated with many tissue-specific developmental disorders. To understand this paradox, we focus on TCOF1, a broadly expressed regulator of rRNA synthesis, whose haploinsufficiency causes Treacher Collins syndrome (TCS). We show that transitional cranial neural crest cells (tCNCC) undergoing mesenchymal specification exhibit extreme dosage-sensitivity to TCOF1, but not to RNA polymerase I, explaining both cellular origins of TCS and prevalence of TCOF1 mutations in the disease. To maintain robust expression, TCOF1 deploys CNCC-specific enhancers that buffer against fluctuations in promoter-regulating factors, converting sensitive expression responses into threshold-protected outputs. Systematic promoter-enhancer coupling experiments demonstrate this principle generalizes across many dosage-sensitive housekeeping genes, whose promoters operate near saturation and only reveal their enhancer-dependency under suboptimal conditions. Thus, enhancers play a unique role at housekeeping promoters: rather than amplifying expression, they ensure its robustness during vulnerable developmental transitions.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "C. Ni"
    },
    {
      "name": "L. Ichino"
    },
    {
      "name": "T. Swigut"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Wysocka"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1x9pxt652ned6.bib",
  "cited_by": 1,
  "doi": "10.64898/2026.07.29.741571",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.07.29.741571v2.full",
  "id": "1x9pxt652ned6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.07.29.741571v2",
  "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",
      "genetics"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7171871090",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.07.29.741571v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1x9pxt652ned6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "10.64898/2026.07.29.741571",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.07.29.741571v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Enhancer buffering protects dosage-sensitive housekeeping genes during vulnerable developmental transitions",
  "title_text": "Enhancer buffering protects dosage-sensitive housekeeping genes during vulnerable developmental transitions",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:35Z",
  "url": "https://research.draconitic.com/paper/1x9pxt652ned6",
  "venue": "bioRxiv",
  "versions": []
}