Chondrocyte-specific enhancer regions in the COMP gene

The molecular events governing the differentiation of mesenchymal cells int o chondrocytes and the expression of cartilage marker genes are poorly unde rstood. Cartilage oligomeric matrix protein is a noncollagenous extracellul ar matrix protein with a relatively cartilage-specific spatial and temporal expression pattern. To understand the mechanisms controlling chondrocyte-s pecific expression of cartilage oligomeric matrix protein, we cloned 1.9 kb of the 5' flanking promoter sequence of the murine cartilage oligomeric ma trix protein gene and identified two spatially distant cartilage-specific e nhancer regions by deletion analysis. One element is situated proximally (p roximal positive element: -125 to -75) and a second region is located dista lly (distal positive region: -1925 to -592) relative to the transcription s tart 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 transc ription factors. Defining cartilage-specific regulatory elements in the car tilage oligomeric matrix protein promoter may provide useful molecular prob es for identifying transcription factors that control acquisition of the ch ondrocytic phenotype.