{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:38:36Z","timestamp":1791081516665,"version":"4.1.0"},"reference-count":46,"publisher":"Portland Press Ltd.","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lysine methyltransferase 2D (KMT2D), as one of the key histone methyltransferases responsible for histone 3 lysine 4 methylation (H3K4me), has been proved to be the main pathogenic gene of Kabuki syndrome disease. Kabuki patients with KMT2D mutation frequently present various dental abnormalities, including abnormal tooth number and crown morphology. However, the exact function of KMT2D in tooth development remains unclear. In this report, we systematically elucidate the expression pattern of KMT2D in early tooth development and outline the molecular mechanism of KMT2D in dental epithelial cell line. KMT2D and H3K4me mainly expressed in enamel organ and Kmt2d knockdown led to the reduction in cell proliferation activity and cell cycling activity in dental epithelial cell line (LS8). RNA-sequencing (RNA-seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis screened out several important pathways affected by Kmt2d knockdown including Wnt signaling. Consistently, Top\/Fop assay confirmed the reduction in Wnt signaling activity in Kmt2d knockdown cells. Nuclear translocation of \u03b2-catenin was significantly reduced by Kmt2d knockdown, while lithium chloride (LiCl) partially reversed this phenomenon. Moreover, LiCl partially reversed the decrease in cell proliferation activity and G1 arrest, and the down-regulation of Wnt-related genes in Kmt2d knockdown cells. In summary, the present study uncovered a pivotal role of histone methyltransferase KMT2D in dental epithelium proliferation and cell cycle homeostasis partially through regulating Wnt\/\u03b2-catenin signaling. The findings are important for understanding the role of KMT2D and histone methylation in tooth development.<\/jats:p>","DOI":"10.1042\/bsr20211148","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T11:44:26Z","timestamp":1635767066000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["KMT2D deficiency disturbs the proliferation and cell cycle activity of dental epithelial cell line (LS8) partially via Wnt signaling"],"prefix":"10.1042","volume":"41","author":[{"given":"Liping","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Cariology and Endodontology, School and Hospital of Stomatology, Peking University, Beijing 100081, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology, School and Hospital of Stomatology, Peking University, Beijing 100081, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology, School and Hospital of Stomatology, Peking University, Beijing 100081, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology, School and Hospital of Stomatology, Peking University, Beijing 100081, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9981-7592","authenticated-orcid":false,"given":"Zhichun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology, School and Hospital of Stomatology, Peking University, Beijing 100081, P.R. 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