Ducy P, Geoffroy V, Karsenty G
Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Connect Tissue Res. 1996;35(1-4):7-14. doi: 10.3109/03008209609029169.
In an attempt to understand the mechanisms of osteoblast-specific expression, we analyzed the promoter of the mouse osteocalcin gene 2, an osteoblast-specific gene. In this promoter, using a combination of DNA transfection experiments and DNA binding assays, we have identified two osteoblast-specific cis-acting elements called OSE1 and OSE2. Inspection of OSE2 DNA sequence and site-specific mutagenesis allowed us to define a core sequence for OSE2. This core sequence is identical to the DNA binding site of the PEBP2 alpha transcription factors, the mouse homologues of the Drosophila Runt protein. Here we show that OSF2, the factor present in osteoblast nuclear extracts and binding to OSE2, is immunologically related to the PEBP2 alpha transcription factors. In DNA cotransfection experiment, a human homologue of PEBP2 alpha transcription factor increases the activity of a short osteocalcin promoter through its binding to OSE2. Thus, this study presents evidence that OSF2 is a member of the PEBP2 alpha family of transcription factors.
为了了解成骨细胞特异性表达的机制，我们分析了小鼠骨钙素基因2（一种成骨细胞特异性基因）的启动子。在该启动子中，通过结合DNA转染实验和DNA结合分析，我们鉴定出了两个成骨细胞特异性顺式作用元件，分别称为OSE1和OSE2。对OSE2 DNA序列的检查和位点特异性诱变使我们能够确定OSE2的核心序列。该核心序列与PEBP2α转录因子的DNA结合位点相同，PEBP2α转录因子是果蝇Runt蛋白的小鼠同源物。在此我们表明，存在于成骨细胞核提取物中并与OSE2结合的因子OSF2在免疫学上与PEBP2α转录因子相关。在DNA共转染实验中，PEBP2α转录因子的人类同源物通过与OSE2结合来增加短骨钙素启动子的活性。因此，本研究提供了证据表明OSF2是PEBP2α转录因子家族的成员。
