Chondrocyte-specific enhancer regions in the COMP gene

The molecular events governing the differentiation of mesenchymal cells into chondrocytes and the expression of cartilage marker genes are poorly understood. Cartilage oligomeric matrix protein is a noncollagenous extracellular matrix protein with a relatively cartilage-specific spatial and temporal expression pattern. To understand the mechanisms controlling chondrocyte-specific expression of cartilage oligomeric matrix protein, we cloned 1.9 kb of the 5' flanking promoter sequence of the murine cartilage oligomeric matrix protein gene and identified two spatially distant cartilage-specific enhancer regions by deletion analysis. One element is situated proximally (proximal positive element: -125 to -75) and a second region is located distally (distal positive region: -1925 to -592) relative to the transcription start site. Interestingly, nucleotides within the proximal positive element are conserved between the mouse and human promoters and resemble consensus sites for the binding of members of the high mobility group class of transcription factors. Defining cartilage-specific regulatory elements in the cartilage oligomeric matrix protein promoter may provide useful molecular probes for identifying transcription factors that control acquisition of the chondrocytic phenotype.