Trichostatin A activates the osteopontin gene promoter through AP1 site.
In this study, we investigated osteoblastic differentiation by trichostatin A (TSA), a histone deacetylase inhibitor in mouse undifferentiated mesenchymal cell line. TSA increased the osteopontin (OPN) mRNA level and OPN protein. Deletion analysis of the promoter region revealed TSA-induced luciferase response was regulated by -75 to -65 of the OPN promoter. There was an AP1-binding sequence at the site of the OPN promoter. In an electrophoretic mobility shift assay, bands of the complexes were supershifted by addition of antibody to c-fos and phosphorylated c-jun. These data suggested that AP1 plays a crucial role in the TSA-induced OPN expression.
Department of Orthopedic Surgery, Wakayama Medical University, 811-1, Wakayama 641-8510, Japan. ryosuke@wakayama-med.ac.jp
Ryosuke
R
Sakata
Shinji
S
Minami
Yoshihiro
Y
Sowa
Munehito
M
Yoshida
Tetsuya
T
Tamaki
D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D002460:Cell Line; D004252:DNA Mutational Analysis / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D053495:Osteopontin; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D018808:Transcription Factor AP-1; D053495:Osteopontin; C012589:trichostatin A; D008156:Luciferases