title: Scleraxis and E47 cooperatively regulate the Sox9-dependent transcription.
abstract: During musculoskeletal development, Sry-type HMG box 9 (Sox9) has a crucial role in mesenchymal condensation and chondrogenesis. On the other hand, a tissue-specific basic helix-loop-helix (bHLH) transcription factor Scleraxis (Scx) regulates the differentiation of tendon and ligament progenitors. Whereas these two transcription factors cooperatively participate in the determination of cellular lineages, the precise interaction between Sox9 and Scx remains unclear. We have previously demonstrated that the Sox9-dependent transcription is synergistically activated by several Sox9-associating molecules, such as p300 and Smad3, on chromatin. In this study, we investigated the function of Scx in the Sox9-dependent transcription. The expression of alpha1(II) collagen (Col2a1) gene was stimulated by an appropriate transduction of Sox9 and Scx. Scx and its partner E47, which dimerizes with other bHLH proteins, cooperatively enhanced the Sox9-dependent transcription in luciferase reporter assays. Coactivator p300 synergistically increased the activity of Sox9-regulated reporter gene, which contains promoter and enhancer regions of Col2a1, in the presence of Scx and E47. Immunoprecipitation analyses revealed that Scx and E47 formed a transcriptional complex with Sox9 and p300. Scx/E47 heterodimer also associated with a conserved E-box sequence (CAGGTG) in the Col2a1 promoter on chromatin. These findings suggest that Scx and E47 might modulate the primary chondrogenesis by associating with the Sox9-related transcriptional complex, and by binding to the conserved E-box on Col2a1 promoter.
authors.affiliation: Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kitaku, Okayama 700-8558, Japan. matino@md.okayama-u.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Furumatsu
authors.forename: Chisa
authors.initials: C
authors.lastname: Shukunami
authors.forename: Michiyo
authors.initials: M
authors.lastname: Amemiya-Kudo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D024721:E-Box Elements / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000378:metabolism*; D058125:Transcription Factor 7-Like 1 Protein; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024043:Collagen Type II; D050881:E1A-Associated p300 Protein; D055758:SOX9 Transcription Factor; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; C499177:COL2A1 protein, human; C093504:SCX protein, human; C503815:Scx protein, mouse; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; C494360:EP300 protein, human