{
  "id": 12202952,
  "title": "Distinct sequence grammars of nucleosomal and linker DNA shape mutational and methylation landscapes in cancer",
  "url": "https://urgent.news/2026/10/04/distinct-sequence-grammars-of-nucleosomal-and-linker-dna-shape",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-04T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755196v1?rss=1"
  },
  "original_language": "en",
  "account": "Nucleosomes, which regulate DNA accessibility and impact gene expression, DNA repair, and mutagenesis, have a higher-order sequence grammar underlying nucleosome organization. This grammar's relationship to cancer-associated mutational and epigenetic processes has been unclear.\n\nResearchers have developed DeepND, an interpretable deep learning framework that can distinguish nucleosomal from inter-nucleosomal DNA and identify sequence features related to nucleosome architecture. This framework revealed 210 sequence motifs, 2-16 base pairs long, that were significantly enriched or depleted in nucleosomal DNA, expanding upon previously known nucleosomal motifs.\n\nAmong these motifs, 44 were associated with cancer-type-specific enrichment or depletion of somatic mutations, while six were linked to differential DNA methylation levels. In lung and endometrial cancers, mutations showed a notable ~10-base pair periodic enrichment pattern across various minor-groove orientations, suggesting differential sensitivity of mutational and DNA repair processes to nucleosomal rotational positioning.\n\nFurthermore, sequence-specific methylation patterns were identified, indicating reduced accessibility of nucleosomal DNA to DNA methyltransferases. This included differential methylation at both inward- and outward-facing CpG motifs. In summary, this study provides a sequence-resolved characterization of nucleosome-level organization and its connection to cancer-specific mutational processes and epigenetic landscapes.",
  "summary": "Nucleosomes regulate DNA accessibility and thereby influence gene expression, DNA repair, and mutagenesis. Although DNA sequence strongly determines nucleosome positioning, the higher-order sequence grammar underlying nucleosome organization and its relationship to cancer-associated mutational and epigenetic processes remain poorly understood. We developed DeepND, an interpretable deep learning…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}