The histone H3K9 methyltransferase G9a regulates tendon formation during development

被引：0
作者：
Satoshi Wada [1 ]
Hisashi Ideno [2 ]
Kazuhisa Nakashima [3 ]
Koichiro Komatsu [1 ]
Noboru Demura [1 ]
Hiroshi Tomonari [1 ]
Hiroshi Kimura [2 ]
Makoto Tachibana [3 ]
Akira Nifuji [4 ]
机构：
[1] Department of Pharmacology, School of Dental Medicine, Tsurumi University, Kanagawa, Yokohama
[2] Department of Oral and Maxillofacial Surgery, School of Medicine, Kanazawa Medical University, Ishikawa, Uchinada
[3] Department of Orthodontics, School of Dental Medicine, Tsurumi University, Kanagawa, Yokohama
[4] Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa, Yokohama
[5] Laboratory of Epigenome Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Suita
来源：
Scientific Reports | / 14卷 / 1期
基金：
日本学术振兴会;
关键词：
Cell differentiation; Epigenetics; Histone modification; Proliferation; Tenocytes;
D O I：
10.1038/s41598-024-71570-5
中图分类号：
学科分类号：
摘要：
G9a is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9 (H3K9), which is involved in the regulation of gene expression. We had previously reported that G9a is expressed in developing tendons in vivo and in vitro and that G9a-deficient tenocytes show impaired proliferation and differentiation in vitro. In this study, we investigated the functions of G9a in tendon development in vivo by using G9a conditional knockout (G9a cKO) mice. We crossed Sox9Cre/+ mice with G9afl/fl mice to generate G9afl/fl; Sox9Cre/+ mice. The G9a cKO mice showed hypoplastic tendon formation at 3 weeks of age. Bromodeoxyuridine labeling on embryonic day 16.5 (E16.5) revealed decreased cell proliferation in the tenocytes of G9a cKO mice. Immunohistochemical analysis revealed decreased expression levels of G9a and its substrate, H3K9me2, in the vertebral tendons of G9a cKO mice. The tendon tissue of the vertebrae and limbs of G9a cKO mice showed reduced expression of a tendon marker, tenomodulin (Tnmd), and col1a1 genes, suggesting that tenocyte differentiation was suppressed. Overexpression of G9a resulted in enhancement of Tnmd and col1a1 expression in tenocytes in vitro. These results suggest that G9a regulates the proliferation and differentiation of tendon progenitor cells during tendon development. Thus, our results suggest that G9a plays an essential role in tendon development. © The Author(s) 2024.
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