Functional Hierarchy between Two OSE2 Elements in the Control of Osteocalcin Gene Expression in Vivo

Osteocalcin gene expression is initiated perinatally and is restricted to mature osteoblasts and odontoblasts. Because their pattern of expression is highly restricted, the osteocalcin genes are excellent tools to study osteoblast-specific gene expression. To define the mechanisms of osteocalcin cel...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-11, Vol.273 (46), p.30509-30516
Main Authors: Frendo, Jean-Louis, Xiao, Guozhi, Fuchs, Sebastien, Franceschi, Renny T., Karsenty, Gerard, Ducy, Patricia
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Cells, Cultured
Gene Expression
Genes, Reporter
Lac Operon
Mice
Mice, Transgenic
Osteoblasts - cytology
Osteocalcin - genetics
Promoter Regions, Genetic
Space life sciences
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Summary:Osteocalcin gene expression is initiated perinatally and is restricted to mature osteoblasts and odontoblasts. Because their pattern of expression is highly restricted, the osteocalcin genes are excellent tools to study osteoblast-specific gene expression. To define the mechanisms of osteocalcin cell-specific gene expression in vivo, we generated transgenic mice harboring deletion mutants of the promoter region of OG2, one of the mouse osteocalcin genes. We show here that only 647 base pairs of this promoter are sufficient to confer cell-specific and time-specific expression to a reporter gene in vivo. This promoter fragment contains two copies of OSE2. This osteoblast-specificcis-acting element binds Osf2, a recently characterized osteoblast-specific transcription factor (Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., and Karsenty, G. (1997)Cell 89, 747–754). We also demonstrate that the proximal OSE2 element is critical to confer an osteoblast-specific, developmentally regulated pattern of expression to a reporter gene. The other OSE2 element, located more upstream and presenting a lower affinity for Osf2, affects only weakly OG2 promoter activity. These data demonstrate the crucial role of Osf2 in controlling osteocalcin gene expression. Since osteocalcin synthesis is a hallmark of the differentiated osteoblast phenotype, these results suggest that, beyond its developmental function, Osf2 is also required for the maintenance of the osteoblast phenotype postnatally.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.46.30509