Proximal promoter binding protein contributes to developmental, tissue-restricted expression of the rat osteocalcin gene
Arianne A. J. Heinrichs
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorRita Bortell
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorMichael Bourke
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorJane B. Lian
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorGary S. Stein
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorJanet L. Stein
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorArianne A. J. Heinrichs
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorRita Bortell
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorMichael Bourke
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorJane B. Lian
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorGary S. Stein
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorJanet L. Stein
Department of Cell Biology and Comprehensive Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0106
Search for more papers by this authorAbstract
Osteocalcin is a 6 kD tissue-specific calcium binding protein associated with the bone extracellular matrix. The osteocalcin gene is developmentally expressed in postproliferative rat osteoblasts with regulation at least in part at the transcriptional level. Multiple, basal promoter and enhancer elements which control transcriptional activity in response to physiological mediators, including steroid hormones, have been identified in the modularly organized osteocalcin gene promoter. The osteocalcin box (OC box) is a highly conserved basal regulatory element residing between nucleotides −99 and −76 of the proximal promoter. We recently established by in vivo competition analysis that protein interactions at the CCAAT motif, which is the central core of the rat OC box, are required for support of basal transcription [Heinrichs et al. J Cell Biochem 53:240–250, 1993]. In this study, by the combined utilization of electrophoretic mobility shift analysis, UV cross linking, and DNA affinity chromatography, we have identified a protein that binds to the rat OC box. Results are presented that support involvement of the OC box-binding protein in regulating selective expression of the osteocalcin gene during differentiation of the rat osteoblast phenotype and suggest that this protein is tissue restricted.
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