title: Osterix induces Col1a1 gene expression through binding to Sp1 sites in the bone enhancer and proximal promoter regions.
abstract: Bone-specific transcription factors promote differentiation of mesenchymal precursors toward the osteoblastic cell phenotype. Among them, Runx2 and Osterix have been widely accepted as master osteogenic factors, since neither Runx2 nor Osterix null mice form mature osteoblasts. Recruitment of Osterix to a number of promoters of bone-specific genes has been shown. However, little is known about the functional interactions between Osterix and the Col1a1 promoter. In this study we determined in several mesenchymal and osteoblastic cell types that either BMP-2 or Osterix overexpression increased Col1a1 transcription. We identified consensus Sp1 sequences, located in the proximal promoter and in the bone-enhancer, as Osterix binding regions in the Col1a1 promoter in vitro and in vivo. Furthermore, we show that p38 or Erk MAPK signaling is required for maximal transcriptional effects on Col1a1 expression. Runx2 has been shown to activate Col1a1 expression through binding to sites which are located close to the Sp1 sites where Osterix binds. Our data show that overexpression of Runx2 and Osterix leads to a cooperative effect on the expression of the Col1a1 endogenous gene and its promoter reporter construct. These effects mainly affect the long isoform of Osterix which suggest that the two Osterix isoforms might display some differential effects on the transactivation of bone-specific genes.
authors.affiliation: Departament de Ciències Fisiològiques II, Universitat de Barcelona, IDIBELL, L'Hospitalet de Llobregat, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Ortuño
authors.forename: Antonio R G
authors.initials: AR
authors.lastname: Susperregui
authors.forename: Natalia
authors.initials: N
authors.lastname: Artigas
authors.forename: José Luis
authors.initials: JL
authors.lastname: Rosa
authors.forename: Francesc
authors.initials: F
authors.lastname: Ventura
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D016329:Sp1 Transcription Factor; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases