{
  "abstract": "Centromeric chromatin is defined by the presence of the histone H3 variant CENP-A, which forms a specialized nucleosome required for kinetochore assembly. Compared to canonical H3 nucleosomes, CENP-A nucleosomes exhibit an open DNA conformation that leaves an additional 13 base pairs of DNA accessible at the entry and exit sites. While the CENP-A N-helix has previously been implicated in promoting this enhanced DNA breathing, the contributions of the intrinsically disordered N-terminal tail and adjacent latch regions of CENP-A to nucleosome conformation remain unknown. The intrinsically disordered N-terminal regions of histone H3 are known to facilitate interactions with DNA to stabilize overall nucleosome conformation. Here, we utilized a combination of MNase digestion assays and coarse-grained molecular dynamics simulations of nucleosomes containing targeted swaps of the H3 and CENP-A tail, latch, and N-helix regions to systematically test the contribution of each N-terminal histone region to nucleosomal DNA conformation. Substitution of individual H3 N-terminal regions with those of CENP-A opened the DNA at the entry/exit sites and increased DNA accessibility. While any single CENP-A N-terminal region was sufficient to open the canonical nucleosomal DNA conformation, replacement of any single CENP-A N-terminal region with its H3 counterpart was insufficient to restore the closed DNA conformation characteristic of canonical H3 nucleosomes. Instead, progressive incorporation of multiple H3-derived regions produced increasingly closed DNA conformations, demonstrating that the H3 tail, latch, and N-helices act cooperatively to stabilize wrapped nucleosomal DNA. Taken together, these findings demonstrate that the more restricted DNA breathing of canonical nucleosomes arises from coordinated contributions across multiple N-terminal regions and suggest that the multi-region redundancy in the conformational flexibility of the centromeric nucleosome could emphasize the importance of retaining flexibility in the centromeric nucleosome, even upon post-translational modification and binding to structural proteins.",
  "abstract_shown": true,
  "affiliations": [
    "Medical College of Wisconsin"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "E. A. Paintsil"
    },
    {
      "name": "J. Lee"
    },
    {
      "name": "S. S. Meidl Zahorodny"
    },
    {
      "name": "J. Wereszczynski"
    },
    {
      "affs": [
        0
      ],
      "name": "E. A. Morrison"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/amr8t7e3qm3fk.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.05.15.724335",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.05.15.724335v2.full",
  "id": "amr8t7e3qm3fk",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.05.15.724335v2",
  "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",
      "biophysics"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7161570774",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.05.15.724335v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/amr8t7e3qm3fk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:38Z",
      "native_id": "10.64898/2026.05.15.724335",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.05.15.724335v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Determinants of centromeric nucleosome conformation",
  "title_text": "Determinants of centromeric nucleosome conformation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:38Z",
  "url": "https://research.draconitic.com/paper/amr8t7e3qm3fk",
  "venue": "bioRxiv",
  "versions": []
}