Identification of an osteogenic protein-1 responsive element in the aggrecan promoter.
Previous studies have demonstrated that osteogenic protein-1 (OP-1), a member of the bone morphogenetic protein (BMP) subfamily of the TGF-beta superfamily, stimulates aggrecan synthesis. To investigate transcriptional regulation of the aggrecan gene by OP-1, we constructed a clone containing a 1 kb region of the 5'-upstream sequence of the mouse aggrecan gene fused to the promoter-less luciferase reporter gene in pGL2-Basic vector. A series of promoter deletion constructs were also generated. Studies of the promoter activity of these DNA constructs in transient-transfected cells revealed that deletion of a 33 bp region rendered the promoter unresponsive to OP-1, BMP-6, and CDMP-1 without affecting BMP-2 and TGF-beta1 responsiveness. Thus, the expression of the mouse aggrecan gene in response to BMPs appears to be the result of a unique combination of different cis-acting elements.
Yeh
Lee-Chuan C
LC
Department of Biochemistry, The University of Texas Health Science Center, San Antonio, TX, USA. carolyeh@biochem.uthscsa.edu
Lee
John C
JC
D053674:Aggrecans; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D037181:Lectins, C-Type; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000235:genetics*; D020218:Response Elements; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C508320:Acan protein, mouse; D053674:Aggrecans; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1