Trans-activation of the mouse cartilage-derived retinoic acid-sensitive protein gene by Sox9

J Bone Miner Res. 1999 May;14(5):757-63. doi: 10.1359/jbmr.1999.14.5.757.

Abstract

The transcription factor Sox9 is capable of enhancing type II collagen gene expression and may play a crucial role in chondrogenesis. To determine whether Sox9 is an inducer of the chondrocyte phenotype, we investigated the role of Sox9 in transcription of another cartilage gene encoding the cartilage-derived retinoic acid-sensitive protein (CD-RAP). CD-RAP is specifically expressed during chondrogenesis. We show here that Sox9 protein is able to bind to a SOX consensus sequence in the CD-RAP promoter. Mutation of the SOX motif led to decreased transcription of a CD-RAP promoter construct in chondrocytes. Overexpression of SOX9 resulted in a dose-dependent increased activity of CD-RAP promoter-driven reporter gene in both chondrocytes and nonchondrogenic cells. A truncated SOX9, which contains a binding domain but no trans-activation function, inhibited CD-RAP promoter activity. Overexpression of SOX9 increased the level of endogenous CD-RAP mRNA in chondrocytes, but was unable to induce endogenous gene expression in 10T1/2 mesenchymal cells or BALB/c-3T3 fibroblasts. These results suggest that Sox9 is a general transcriptional regulator of cartilage-specific genes. However, Sox9 does not appear to be able to induce the chondrocyte phenotype in nonchondrogenic cells, implying that other factors are involved in chondrogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cartilage / metabolism*
  • Cells, Cultured
  • Chondrocytes / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Extracellular Matrix Proteins
  • Gene Expression Regulation, Developmental
  • High Mobility Group Proteins / genetics*
  • High Mobility Group Proteins / metabolism
  • Mice
  • Nuclear Proteins*
  • Phenotype
  • Promoter Regions, Genetic
  • Proteins / genetics
  • Proteins / metabolism*
  • SOX9 Transcription Factor
  • Sex-Determining Region Y Protein
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation*
  • Tretinoin / metabolism*

Substances

  • DNA-Binding Proteins
  • Extracellular Matrix Proteins
  • High Mobility Group Proteins
  • Mia protein, mouse
  • Nuclear Proteins
  • Proteins
  • SOX9 Transcription Factor
  • Sex-Determining Region Y Protein
  • Sox9 protein, mouse
  • Transcription Factors
  • Tretinoin
  • DNA