Histone demethylase Utx regulates differentiation and mineralization in osteoblasts.
Alteration of methylation status of lysine 27 on histone H3 (H3K27) associates with dramatic changes in gene expression in response to various differentiation signals. Demethylation of H3K27 is controlled by specific histone demethylases including ubiquitously transcribed tetratricopeptide repeat X chromosome (Utx). However, the role of Utx in osteoblast differentiation remains unknown. In this study, we examined whether Utx should be involved in osteoblast differentiation. Expression of Utx increased during osteoblast differentiation in MC3T3-E1 cells and primary osteoblasts. GSK-J1, a potent inhibitor of H3K27 demethylase, increased the levels of trimethylated H3K27 (H3K27me3) and decreased the expressions of Runx2 and Osterix and ALP activity in MC3T3-E1 cells. Stable knockdown of Utx by shRNA attenuated osteoblast differentiation and decreased ALP activity, calcium content, and bone-related gene expressions. Silencing of Utx increased the level of H3K27me3 on the promoter regions of Runx2 and Osterix and decreased the promoter activities of Runx2 and Osterix. Taken together, our present results propose that Utx plays important roles in osteoblast differentiation by controlling the expressions of Runx2 and Osterix.
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8504, Japan.|Department of Endodontics, School of Stomatology, China Medical University, Shenyang, 110002, China.
Di
D
Yang
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8504, Japan.
Hirohiko
H
Okamura
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8504, Japan.
Jumpei
J
Teramachi
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8504, Japan.
Tatsuji
T
Haneji
D000818:Animals; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056466:Histone Demethylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics*
D050659:Core Binding Factor Alpha 1 Subunit; D004791:Enzyme Inhibitors; D006657:Histones; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D056466:Histone Demethylases; C111778:Utx protein, mouse
H3K27ME3; HISTONE DEMETHYLATION; OSTEOBLAST DIFFERENTIATION; OSTERIX; RUNX2; Utx