{
  "abstract": "In mammals, DNA methylation is an essential inheritable epigenetic modification maintained by the DNMT1-UHRF1 machinery in a UHRF1 E3 ubiquitin ligase-activity-dependent manner. UHRF1-catalyzed histone ubiquitination and PAF15 ubiquitination have been proposed to recruit DNMT1 to hemi-methylated CpGs. Here, we confirm that both PAF15 and histone H3 are robustly ubiquitinated by UHRF1 in a replication-dependent manner during S phase. However, loss of PAF15 or its ubiquitination, or overexpression of ubiquitination-deficient PAF15, does not alter DNMT1 recruitment to replicating DNA or global DNA methylation. Notably, the DNMT1 inhibitor GSK-3685032 strongly enhances histone ubiquitination, likely via UHRF1 activation driven by accumulated hemi-methylated CpGs, but markedly reduces PAF15 ubiquitination. We show that UHRF1-mediated PAF15 ubiquitination requires DNMT1, is strictly replication-coupled, and that PAF15 and histone ubiquitination are mediated by distinct UHRF1 pools. Taken together, our study demonstrates that hemi-methylated-DNA-stimulated local histone ubiquitination, rather than replication-coupled PAF15 ubiquitination, drives DNMT1 targeting for maintenance methylation.",
  "abstract_shown": true,
  "affiliations": [
    "Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.",
    "Joint Center for Translational Medicine, Fengxian District Central Hospital, Shanghai, China.",
    "State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.",
    "International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.",
    "Institute of Biochemistry and Biophysics, Warsaw, Poland.",
    "Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. jmweng@bio.ecnu.edu.cn.",
    "Joint Center for Translational Medicine, Fengxian District Central Hospital, Shanghai, China. jmweng@bio.ecnu.edu.cn.",
    "Joint Center for Translational Medicine, Shanghai Fifth People's Hospital, Fudan University and School of Life Sciences, East China Normal University, Shanghai, China. jmweng@bio.ecnu.edu.cn."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jialun Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuanyong Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Meilin Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaoqi Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Fenghua Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Xingrui Song"
    },
    {
      "affs": [
        2
      ],
      "name": "Weiyi Lai"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanling Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhaosu Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Hailin Wang",
      "orcid": "0000-0002-1843-999X"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiwen Li"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Matthias Bochtler",
      "orcid": "0000-0001-7884-4463"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Jiemin Wong",
      "orcid": "0000-0002-5311-842X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d1bysy6da22f6.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77759-8",
  "fulltext_url": "https://europepmc.org/articles/PMC13680385",
  "id": "d1bysy6da22f6",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897165",
  "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": [
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7213454062",
  "pdf_url": "https://europepmc.org/articles/PMC13680385?pdf=render",
  "pmcid": "PMC13680385",
  "pmid": "42897165",
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d1bysy6da22f6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897165",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897165"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mammalian DNA maintenance methylation depends on histone but not PAF15 ubiquitination.",
  "title_text": "Mammalian DNA maintenance methylation depends on histone but not PAF15 ubiquitination.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/d1bysy6da22f6",
  "venue": "Nature communications",
  "versions": []
}