The histone H3K9 methyltransferase G9a regulates tendon formation during development

被引：1

作者：

Wada, Satoshi ^{[1
,2
,3
]}

Ideno, Hisashi ^{[1
]}

Nakashima, Kazuhisa ^{[1
]}

Komatsu, Koichiro ^{[1
]}

Demura, Noboru ^{[2
]}

Tomonari, Hiroshi ^{[3
]}

Kimura, Hiroshi ^{[4
]}

Tachibana, Makoto ^{[5
]}

Nifuji, Akira ^{[1
]}

机构：

[1] Tsurumi Univ, Sch Dent Med, Dept Pharmacol, Yokohama, Kanagawa 2308501, Japan

[2] Kanazawa Med Univ, Sch Med, Dept Oral & Maxillofacial Surg, Uchinada, Ishikawa 9200293, Japan

[3] Tsurumi Univ, Sch Dent Med, Dept Orthodont, Yokohama, Kanagawa 2308501, Japan

[4] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Sci, Yokohama, Kanagawa 2268501, Japan

[5] Osaka Univ, Grad Sch Frontier Biosci, Lab Epigenome Dynam, Suita, Osaka 5650871, Japan

来源：

SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期

关键词：

Epigenetics; Histone modification; Tenocytes; Proliferation; Cell differentiation; COORDINATED EXPRESSION; LYSINE METHYLTRANSFERASE; METHYLATION; DIFFERENTIATION; TRANSCRIPTION; MUSCLE; GENE; PROLIFERATION; SOX9; SUPPRESSION;

D O I：

10.1038/s41598-024-71570-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 Sox9(Cre/+) mice with G9a(fl/fl) mice to generate G9a(fl/fl); Sox9(Cre/+) 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.

引用

页数：13

共 62 条

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