{
  "abstract": "Chromatin proteins play critical roles in gene regulation, yet frequently we do not fully understand how weak DNA binding affinity of such proteins contributes to their locus-specific actions. Here, we studied SMCHD1, a non-canonical SMC-family protein involved in three-dimensional genome organization and gene repression of the inactive X chromosome and its autosomal targets. We replaced endogenous SMCHD1 with GFP-tagged wild-type or hinge-domain DNA-binding mutant SMCHD1 to define the cellular role of DNA binding. The mutant showed reduced enrichment at the inactive X chromosome in female cells, while retaining stable binding at most autosomal binding sites. Impaired DNA binding weakens SMCHD1-mediated gene repression and chromatin-state regulation, producing hypomorphic effect. Multiple live-cell imaging methods reveal that DNA binding constrains SMCHD1 mobility and supports maintenance, rather than initial recruitment, of chromatin-bound SMCHD1 both during interphase and mitosis. Thus, SMCHD1's weak and sequence-independent DNA binding is a key determinant of its chromatin residence, localization and function. Our findings provide a framework for understanding SMCHD1 and other chromatin proteins with sequence-independent DNA binding activity.",
  "abstract_shown": true,
  "affiliations": [
    "The Walter and Eliza Hall Institute of Medical Research"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "R. Hu"
    },
    {
      "name": "J. Sanchez-Velasquez"
    },
    {
      "name": "J. Lou"
    },
    {
      "name": "K. Breslin"
    },
    {
      "name": "T. Cameron"
    },
    {
      "name": "A. Solano"
    },
    {
      "name": "I. Wickramasinghe"
    },
    {
      "name": "Q. Gouil"
    },
    {
      "name": "A. J. Kueh"
    },
    {
      "name": "T. Willson"
    },
    {
      "name": "A. Keniry"
    },
    {
      "name": "N. D. Geoghegan"
    },
    {
      "name": "E. Hinde"
    },
    {
      "affs": [
        0
      ],
      "name": "M. E. Blewitt"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1vaybtww0xarf.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.14.751594",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751594v1.full",
  "id": "1vaybtww0xarf",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751594v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7213769265",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751594v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1vaybtww0xarf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:24Z",
      "native_id": "10.64898/2026.09.14.751594",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751594v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "SMCHD1's DNA binding activity enables its stable retention on chromatin",
  "title_text": "SMCHD1's DNA binding activity enables its stable retention on chromatin",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:24Z",
  "url": "https://research.draconitic.com/paper/1vaybtww0xarf",
  "venue": "bioRxiv",
  "versions": []
}