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Publication : A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element.

First Author  Geoffroy V Year  1995
Journal  J Biol Chem Volume  270
Issue  52 Pages  30973-9
PubMed ID  8537354 Mgi Jnum  J:30562
Mgi Id  MGI:78068 Doi  10.1074/jbc.270.52.30973
Citation  Geoffroy V, et al. (1995) A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element. J Biol Chem 270(52):30973-9
abstractText  To identify osteoblast-specific cis-acting elements and trans-acting factors, we initiated an analysis of the promoter of a mouse osteocalcin gene, an osteoblast-specific gene. In this promoter, we identified two osteoblast-specific cis-acting elements (Ducy, P. and Karsenty, G. (1995) Mol. Cell. Biol. 15, 1858-1869). The sequence of one of these elements, OSE2, is identical to the DNA-binding site of the PEBP2 alpha/AML-1 transcription factors, the mammalian homologues of the Drosophila Runt protein. Here we show, using nuclear extracts, recombinant protein, and a specific antiserum against AML-1 proteins in DNA-binding assays, that one member of this family, AML-1B, binds specifically to OSE2 and is immunologically related to OSF2, the factor present in osteoblast nuclear extracts that binds to OSE2. By DNA cotransfection experiments, we also demonstrate that AML-1B can increase the activity of a short osteocalcin promoter through its binding to OSE2. Lastly, the different mobilities of osteoblast nuclear extract-DNA complexes compared with T-cell nuclear extract-DNA complexes, along with the inability of OSF2 to be upregulated by retinoic acid, unlike the other PEBP2 alpha factors, suggest that OSF2 is a new member of this family of transcription factors. Thus, this study demonstrates that AML-1B can increase gene expression of an osteoblast-specific gene through its binding to an osteoblast-specific cis-acting element and presents evidence that OSF2 is a member of the PEBP2 alpha/AML-1 family of transcription factors.
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