title: Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo.
abstract: The alpha1(X) collagen gene (Col10a1) is the only known hypertrophic chondrocyte-specific molecular marker. Until recently, few transcriptional factors specifying its tissue-specific expression have been identified. We show here that a 4-kb murine Col10a1 promoter can drive beta-galactosidase expression in lower hypertrophic chondrocytes in transgenic mice. Comparative genomic analysis revealed multiple Runx2 (Runt domain transcription factor) binding sites within the proximal human, mouse, and chick Col10a1 promoters. In vitro transfection studies and chromatin immunoprecipitation analysis using hypertrophic MCT cells showed that Runx2 contributes to the transactivation of this promoter via its conserved Runx2 binding sites. When the 4-kb Col10a1 promoter transgene was bred onto a Runx2(+/-) background, the reporter was expressed at lower levels. Moreover, decreased Col10a1 expression and altered chondrocyte hypertrophy was also observed in Runx2 heterozygote mice, whereas Col10a1 was barely detectable in Runx2-null mice. Together, these data suggest that Col10a1 is a direct transcriptional target of Runx2 during chondrogenesis.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zheng
authors.forename: Guang
authors.initials: G
authors.lastname: Zhou
authors.forename: Roy
authors.initials: R
authors.lastname: Morello
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Xavier
authors.initials: X
authors.lastname: Garcia-Rojas
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D024121:Collagen Type X / Q000235:genetics* / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005269:Femur / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006811:Humerus / Q000166:cytology / Q000378:metabolism; D006984:Hypertrophy; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D014157:Transcription Factors