{
  "abstract": "Selective occupancy of chromatin-regulatory complexes is central to developmental gene regulation, yet the sequence determinants of this selectivity remain poorly understood. Using interpretable machine learning, we identify a composite promoter architecture comprising CpG islands flanked by several-kilobase A/T-rich domains (AT-flanks) that denotes high occupancy of the Menin-KMT2A histone-modifying complex at developmental and leukemia-associated genes. Genetic deletion and chromatin-contact analyses show that AT-flanks support KMT2A retention at linked CpG islands. We identify LEDGF as an A/T-rich DNA-associated protein required for Menin engagement at AT-flanks and sustained KMT2A promoter occupancy. AT-flank extent is associated with differential KMT2A loss following pharmacologic disruption of the Menin-KMT2A interaction, providing a genomic basis for heterogeneous target sensitivity to recently approved Menin inhibitors in acute leukemia. Beyond Menin-KMT2A, the same architecture distinguishes promoters with high canonical PRC1 occupancy across diverse cell types, revealing a shared sequence organization associated with distinct chromatin-regulatory states.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "P. R. Freire"
    },
    {
      "name": "B. Regalado"
    },
    {
      "name": "R. Takeda"
    },
    {
      "name": "E. T. Ener"
    },
    {
      "name": "G. Wan"
    },
    {
      "name": "J. A. Cutler"
    },
    {
      "name": "T. Z. Baharav"
    },
    {
      "name": "J. Brown"
    },
    {
      "name": "V. Sharlandjieva"
    },
    {
      "name": "T. Milne"
    },
    {
      "name": "R. A. Irizarry"
    },
    {
      "affs": [
        0
      ],
      "name": "S. A. Armstrong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bgwcfdjx0g2h2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.30.763078",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763078v1.full",
  "id": "bgwcfdjx0g2h2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763078v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763078v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bgwcfdjx0g2h2.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T00:20:36Z",
      "native_id": "10.64898/2026.10.30.763078",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763078v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A Unique Promoter Architecture Defines Menin-KMT2A Complex Selectivity",
  "title_text": "A Unique Promoter Architecture Defines Menin-KMT2A Complex Selectivity",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:02Z",
  "url": "https://research.draconitic.com/paper/bgwcfdjx0g2h2",
  "venue": "bioRxiv",
  "versions": []
}