{
  "abstract": "Enhancers integrate combinatorial inputs from sequence-specific transcription factors (TFs) and their activity must be calibrated to achieve precise spatiotemporal control of transcript dosage. Here we demonstrate that the sequence-specific repressors SNAI1 and SNAI2 (i.e. SNAIL and SLUG) quantitatively tune enhancer activity. In human neural crest cells, SNAI1/2 occupy a subset of active enhancers, where their depletion increases H3K27ac, chromatin accessibility, and enhancer regulatory potential. Changes in SNAI1/2 binding motifs contribute to enhancer divergence between human and chimpanzee, suggesting an evolutionary role for the repressor-mediated tuning. Single-molecule chromatin profiling using Deaminase-Assisted Fiber-seq (DAF-seq) reveals that individual enhancers toggle between an ensemble of open and nucleosome-dense chromatin states. While transcriptional activators increase the fraction of the open states, SNAI1/2 shift the equilibrium toward nucleosome-occupied states. This impedes binding of activator TFs, without fully repressing the enhancer. We propose that SNAI1/2 function as a molecular dimmer switch, modulating nucleosome dynamics to calibrate enhancer output.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "L. Ichino"
    },
    {
      "name": "K. J. Brennan"
    },
    {
      "name": "B. J. Mallory"
    },
    {
      "name": "T. Swigut"
    },
    {
      "name": "S. C. Bohaczuk"
    },
    {
      "name": "J. Mohammed"
    },
    {
      "name": "D. G. Mudeppa"
    },
    {
      "name": "S. Tabatabaee"
    },
    {
      "name": "C. Ni"
    },
    {
      "name": "A. B. Stergachis"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Wysocka"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fr6bcjjw0fevt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.11.751074",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751074v1.full",
  "id": "fr6bcjjw0fevt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751074v1",
  "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",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7213202344",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751074v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fr6bcjjw0fevt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:21Z",
      "native_id": "10.64898/2026.09.11.751074",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751074v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Enhancer Tuning by Sequence-Specific Repressors",
  "title_text": "Enhancer Tuning by Sequence-Specific Repressors",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:21Z",
  "url": "https://research.draconitic.com/paper/fr6bcjjw0fevt",
  "venue": "bioRxiv",
  "versions": []
}