{
  "abstract": "Background\n\nOrofacial clefts, particularly cleft palate, are among the most common congenital anomalies, imposing substantial functional impairment and psychosocial burden on affected individuals. Emerging evidence implicates epigenetic modifications, especially histone lysine methylation, as critical regulators of embryonic development, yet their precise roles in palatogenesis remain poorly defined. The H3K4 methyltransferase complexes, which require the core subunit ASH2L for full enzymatic activity, govern transcriptional activation during development; however, whether ASH2L-mediated H3K4me3 deposition contributes to palatal morphogenesis is unknown.Results\n\nHere, we show that conditional deletion of Ash2l in Six2-positive palatal mesenchymal cells results in complete cleft palate in mice. Multi-omics analyses (RNA-seq and CUT&Tag-seq) reveal that Ash2l loss causes genome-wide reduction of H3K4me3 enrichment at key developmental genes, most notably Wnt5b, leading to their transcriptional downregulation. Functionally, Ash2l deficiency impairs proliferation and osteogenic differentiation of palatal mesenchymal cells, resulting in stunted palatal shelf growth and disrupted osteogenesis. Pharmacological activation of WNT signaling downstream of Wnt5b partially rescues these cellular defects, confirming the functional relevance of this axis.Conclusion\n\nThese findings establish ASH2L-mediated H3K4me3 as a critical epigenetic regulator of palatal development through WNT5B modulation, and identify potential therapeutic targets for cleft palate.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
    "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.",
    "National Center for Stomatology, Shanghai, China.",
    "National Clinical Research Center for Oral Diseases, Shanghai, China.",
    "Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.",
    "Department of Pediatric Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xfr1988@163.com.",
    "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China. xfr1988@163.com.",
    "National Center for Stomatology, Shanghai, China. xfr1988@163.com.",
    "National Clinical Research Center for Oral Diseases, Shanghai, China. xfr1988@163.com.",
    "Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China. xfr1988@163.com.",
    "Department of Pediatric Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wangjun202@126.com.",
    "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China. wangjun202@126.com.",
    "National Center for Stomatology, Shanghai, China. wangjun202@126.com.",
    "National Clinical Research Center for Oral Diseases, Shanghai, China. wangjun202@126.com.",
    "Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China. wangjun202@126.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Zhichen Ling"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Xueqin Zhu"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Xinyi Tan"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Zhangke Ma"
    },
    {
      "affs": [
        5,
        6,
        7,
        8,
        9
      ],
      "name": "Furong Xie"
    },
    {
      "affs": [
        10,
        11,
        12,
        13,
        14
      ],
      "name": "Jun Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5re2j9t06expc.bib",
  "cited_by": 0,
  "doi": "10.1186/s13072-026-00690-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13685272",
  "id": "5re2j9t06expc",
  "issns": [
    "1756-8935"
  ],
  "landing_url": "https://europepmc.org/article/MED/42902390",
  "language": "eng",
  "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": [
    [
      "lcc",
      "QH426-470"
    ],
    [
      "openalex",
      "1311|Cleft Lip and Palate Research"
    ]
  ],
  "openalex": "W7170293175",
  "pdf_url": "https://europepmc.org/articles/PMC13685272?pdf=render",
  "pmcid": "PMC13685272",
  "pmid": "42902390",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/5re2j9t06expc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42902390",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42902390"
    },
    {
      "first_seen": "2026-10-30T13:46:29Z",
      "native_id": "f0dab25b06aa4093a04fc4904ee37fbf",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s13072-026-00690-1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Cleft Lip and Palate Research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "ASH2L-mediated H3K4me3 methylation governs palatal development by regulating WNT5B.",
  "title_text": "ASH2L-mediated H3K4me3 methylation governs palatal development by regulating WNT5B.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:29Z",
  "url": "https://research.draconitic.com/paper/5re2j9t06expc",
  "venue": "Epigenetics & chromatin",
  "versions": []
}