{
  "abstract": "Centromere identity is specified by CENP-A, a histone H3 variant that epigenetically defines centromere position. How CENP-A is maintained at one location in rapidly evolving centromeric DNA is unknown. Using single-cell-derived clones of human cell lines, we demonstrate heterogeneity in CENP-A position within cell populations at neocentromeres and a native centromere. CENP-A heterogeneity is accompanied by heterogeneous DNA methylation patterns, with DNA methylation shifting according to CENP-A position. We demonstrate centromere epigenetic plasticity over extended proliferation, with native centromeres maintaining stable DNA methylation boundaries, but neocentromeres exhibiting DNA methylation instability, boundary loss, and increased missegregation. Finally, we show that neocentromeres are more sensitive to DNA methylation inhibition than native centromeres, and that this inhibition is accompanied by expanded CENP-A-enriched domains and increased missegregation. This study supports a role for DNA methylation boundaries in maintaining centromere position, stability, and function and highlights the intrinsic instability of DNA methylation at neocentromeres.",
  "abstract_shown": true,
  "affiliations": [
    "UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA",
    "Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA",
    "Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA; Department of Genetics and Genome Sciences, UConn Health, Farmington CT, USA",
    "Somatic Genomics Programme, Wellcome Sanger Institute, Hinxton, UK",
    "UC Santa Cruz Genomics Institute, Santa Cruz, CA, USA",
    "Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA",
    "Department of Genetics and Genome Sciences, UConn Health, Farmington CT, USA",
    "Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA",
    "UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: arbelyy@upmc.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Megan A. Mahlke"
    },
    {
      "affs": [
        0
      ],
      "name": "Angela Enriquez",
      "orcid": "0009-0009-8264-3766"
    },
    {
      "affs": [
        0
      ],
      "name": "Lior Lumerman"
    },
    {
      "affs": [
        0
      ],
      "name": "Poulomi Nath",
      "orcid": "0000-0002-1063-5427"
    },
    {
      "affs": [
        1
      ],
      "name": "Cy Chittenden",
      "orcid": "0009-0006-6357-2315"
    },
    {
      "affs": [
        2
      ],
      "name": "Savannah J. Hoyt",
      "orcid": "0000-0001-7804-3236"
    },
    {
      "affs": [
        3
      ],
      "name": "Jonas Koeppel",
      "orcid": "0000-0003-1306-3994"
    },
    {
      "affs": [
        4
      ],
      "name": "Yuan Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Rebecca Raphael"
    },
    {
      "affs": [
        0
      ],
      "name": "Kylie Zaffina"
    },
    {
      "affs": [
        5
      ],
      "name": "Paul W. Hook",
      "orcid": "0000-0002-3912-1999"
    },
    {
      "affs": [
        5
      ],
      "name": "Winston Timp",
      "orcid": "0000-0003-2083-6027"
    },
    {
      "affs": [
        4
      ],
      "name": "Karen H. Miga",
      "orcid": "0000-0002-3670-4507"
    },
    {
      "affs": [
        3
      ],
      "name": "Peter J. Campbell"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Rachel J. O’Neill"
    },
    {
      "affs": [
        1
      ],
      "name": "Nicolas Altemose",
      "orcid": "0000-0002-7231-6026"
    },
    {
      "affs": [
        8
      ],
      "name": "Yael Nechemia‐Arbely",
      "orcid": "0000-0001-5753-5485"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5fb9pjvjptt4e.bib",
  "cited_by": 10,
  "doi": "10.1016/j.celrep.2026.117770",
  "fulltext_url": null,
  "id": "5fb9pjvjptt4e",
  "issns": [
    "2211-1247",
    "2639-1856"
  ],
  "landing_url": "https://doi.org/10.1016/j.celrep.2026.117770",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
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  "openalex": "W7196971800",
  "pdf_url": null,
  "pmcid": "PMC11838504",
  "pmid": "39975122",
  "published": "2026-08-01",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/5fb9pjvjptt4e.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:07Z",
      "native_id": "W7196971800",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.celrep.2026.117770"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Neocentromeres fail to maintain DNA methylation boundaries, driving CENP-A drift, instability, and chromosome missegregation",
  "title_text": "Neocentromeres fail to maintain DNA methylation boundaries, driving CENP-A drift, instability, and chromosome missegregation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:30Z",
  "url": "https://research.draconitic.com/paper/5fb9pjvjptt4e",
  "venue": "Cell Reports",
  "versions": []
}