title: Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription.
abstract: SRY-box-containing gene 9 (Sox9) is an essential transcription factor in chondrocyte lineage determination and differentiation. Recent studies demonstrated that Sox9 controls the transcription of chondrocyte-specific genes in association with several other transcriptional regulators. To further understand the molecular mechanisms by which Sox9 influences transcriptional events during chondrocyte differentiation, we attempted to identify transcriptional partners of Sox9 and to examine their roles in chondrocyte differentiation. We isolated AT-rich interactive domain-containing protein 5a (Arid5a; also known as Mrf1) as an activator of the Col2a1 gene promoter from an ATDC5 cDNA library. Arid5a was highly expressed in cartilage and induced during chondrocyte differentiation. Furthermore, Arid5a physically interacted with Sox9 in nuclei and up-regulated the chondrocyte-specific action of Sox9. Overexpression of Arid5a stimulated chondrocyte differentiation in vitro and in an organ culture system. In contrast, Arid5a knockdown inhibited Col2a1 expression in chondrocytes. In addition, Arid5a binds directly to the promoter region of the Col2a1 gene and stimulates acetylation of histone 3 in the region. Our results suggest that Arid5a may directly interact with Sox9 and thereby enhance its chondrocyte-specific action.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka 565-0871, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Amano
authors.forename: Kenji
authors.initials: K
authors.lastname: Hata
authors.forename: Shuji
authors.initials: S
authors.lastname: Muramatsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Wakabayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takigawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ono
authors.forename: Masako
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Rikako
authors.initials: R
authors.lastname: Takashima
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Kogo
authors.forename: Akio
authors.initials: A
authors.lastname: Matsuda
authors.forename: Riko
authors.initials: R
authors.lastname: Nishimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D004926:Escherichia coli; D005260:Female; D015870:Gene Expression; D015723:Gene Library; D047908:Intracellular Signaling Peptides and Proteins; D049409:Luciferases, Firefly / Q000032:analysis; D051379:Mice; D009924:Organ Culture Techniques; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D055758:SOX9 Transcription Factor; C464783:Trim59 protein, mouse; D000070584:Tripartite Motif Proteins; D049409:Luciferases, Firefly