{
  "abstract": "Centromeres ensure proper chromosome segregation during cell division, yet the organization and regulation of centromeric chromatin within satellite DNA arrays remain incompletely understood. Here, we leverage the complete diploid human genome benchmark (T2T-HG002) to provide a detailed study of centromeric sequence and chromatin architecture on individual haplotypes. Using adaptive-sampling-enriched, ultra-long-read DiMeLo-seq, we achieve single-molecule chromatin profiling across all centromeres, revealing that along single chromatin fibers, CENP-A, the histone variant specifying centromere identity, forms multiple discrete subdomains within hypomethylated centromere dip regions (CDRs) that are flanked by H3K9me3-enriched heterochromatin. Despite underlying sequence variation, CDRs localize to sequence-homogeneous domains and maintain relatively balanced CENP-A dosage and aggregate length across all chromosomes and between haplotypes. Further, we show that bidirectional changes to centromeric and pericentromeric DNA methylation are accompanied by changes to centromeric chromatin architecture. In passaged cells with centromeric hypomethylation, subdomain boundaries are eroded, and adjacent CENP-A domains tend to merge and expand. Conversely, in pluripotent stem cells with centromeric hypermethylation, CDRs are fundamentally reorganized, such that discrete hypomethylated domains are frequently consolidated into broader contiguous tracts. These methylation-associated CDR restructuring events suggest that DNA methylation acts as a principal regulator of human centromere organization, with implications for understanding centromere plasticity, epigenetic inheritance, and chromosomal instability in development and disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA",
    "UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA; Centre for Biomedical Research and Technology, HSE University, Moscow 101000, Russia; The Center for Bio- and Medical Technologies, Moscow 121205, Russia",
    "UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA; Faculty of Informatics, Masaryk University, 601 77 Brno, Czech Republic",
    "Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA",
    "Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA",
    "UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA",
    "Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA",
    "Stowers Institute for Medical Research, Kansas City, MO 64110, USA",
    "Coriell Institute for Medical Research, Camden, NJ 08103, USA",
    "Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94305, USA",
    "Department of Biochemistry, Stanford University, Palo Alto, CA 94305, USA",
    "Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, MD 21205, USA",
    "Department of Anatomy and Anthropology & Department of Human Molecular Genetics and Biochemistry, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel",
    "Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Biohub - San Francisco, San Francisco, CA 94158, USA. Electronic address: altemose@stanford.edu",
    "Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address: khmiga@ucsc.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuan Xu",
      "orcid": "0000-0002-7814-7542"
    },
    {
      "affs": [
        0
      ],
      "name": "Hailey Loucks",
      "orcid": "0009-0000-6956-9922"
    },
    {
      "affs": [
        0
      ],
      "name": "Julian M. Menendez",
      "orcid": "0000-0002-0002-8543"
    },
    {
      "affs": [
        1
      ],
      "name": "Fedor Ryabov",
      "orcid": "0000-0001-8728-9465"
    },
    {
      "affs": [
        0
      ],
      "name": "Julian Lucas",
      "orcid": "0000-0001-9163-2756"
    },
    {
      "affs": [
        2
      ],
      "name": "Monika Čechová",
      "orcid": "0000-0002-7420-2663"
    },
    {
      "affs": [
        3
      ],
      "name": "Luke B Morina",
      "orcid": "0000-0003-4728-7152"
    },
    {
      "affs": [
        0
      ],
      "name": "Emily Xu"
    },
    {
      "affs": [
        4
      ],
      "name": "Danilo Dubocanin",
      "orcid": "0000-0003-0330-5814"
    },
    {
      "affs": [
        4
      ],
      "name": "Cy Chittenden",
      "orcid": "0009-0006-6357-2315"
    },
    {
      "affs": [
        0
      ],
      "name": "Mobin Asri",
      "orcid": "0000-0002-7194-5138"
    },
    {
      "affs": [
        5
      ],
      "name": "Ivo Violich"
    },
    {
      "affs": [
        6
      ],
      "name": "Christian Ortiz"
    },
    {
      "affs": [
        5
      ],
      "name": "Joshua M.V. Gardner"
    },
    {
      "affs": [
        5
      ],
      "name": "Todd L. Hillaker"
    },
    {
      "affs": [
        0
      ],
      "name": "Sara O'Rourke"
    },
    {
      "affs": [
        5
      ],
      "name": "Brandy McNulty"
    },
    {
      "affs": [
        7
      ],
      "name": "Tamara Potapova",
      "orcid": "0000-0003-2761-1795"
    },
    {
      "affs": [
        8
      ],
      "name": "Matthew W. Mitchell",
      "orcid": "0000-0002-6947-0495"
    },
    {
      "affs": [
        9
      ],
      "name": "Jacob Price Schwartz",
      "orcid": "0000-0003-1064-7193"
    },
    {
      "affs": [
        10
      ],
      "name": "Aaron F. Straight",
      "orcid": "0000-0001-5885-7881"
    },
    {
      "affs": [
        7
      ],
      "name": "Jennifer L. Gerton",
      "orcid": "0000-0003-0743-3637"
    },
    {
      "affs": [
        11
      ],
      "name": "Winston Timp",
      "orcid": "0000-0003-2083-6027"
    },
    {
      "affs": [
        12
      ],
      "name": "Ivan A. Alexandrov",
      "orcid": "0000-0003-4342-2003"
    },
    {
      "affs": [
        13
      ],
      "name": "Nicolas Altemose",
      "orcid": "0000-0002-7231-6026"
    },
    {
      "affs": [
        14
      ],
      "name": "Karen H. Miga",
      "orcid": "0000-0002-3670-4507"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/14wm98vtcy9n4.bib",
  "cited_by": 6,
  "doi": "10.1016/j.xgen.2026.101324",
  "fulltext_url": null,
  "id": "14wm98vtcy9n4",
  "issns": [
    "2666-979X"
  ],
  "landing_url": "https://doi.org/10.1016/j.xgen.2026.101324",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1110|Chromosomal and Genetic Variations"
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  "openalex": "W7196934772",
  "pdf_url": null,
  "pmcid": "PMC13060124",
  "pmid": "41959200",
  "published": "2026-08-01",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/14wm98vtcy9n4.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:08Z",
      "native_id": "W7196934772",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.xgen.2026.101324"
    }
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1110|Chromosomal and Genetic Variations",
      "subfield": "plant-biology"
    }
  ],
  "title": "Haplotype-resolved DiMeLo-seq maps centromeric chromatin in a complete diploid human genome",
  "title_text": "Haplotype-resolved DiMeLo-seq maps centromeric chromatin in a complete diploid human genome",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:32Z",
  "url": "https://research.draconitic.com/paper/14wm98vtcy9n4",
  "venue": "Cell Genomics",
  "versions": []
}