Theofan G, Haberstroh L M, Price P A
Department of Biology, University of California, San Diego, La Jolla 92093.
DNA. 1989 Apr;8(3):213-21. doi: 10.1089/dna.1.1989.8.213.
The rat bone Gla protein (BGP, osteocalcin) gene was isolated from a rat genomic library and sequenced. BGP is a 5.8-kD noncollagenous protein secreted by calcified tissues whose expression is regulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The BGP gene consists of 4 exons separated by 3 introns and spans almost 1 kb of DNA. The 5'-flanking region of the gene contains CCAAT and TATAAA elements common to eukaryotic genes. An analysis of approximately 600 bp of 5'-flanking sequence of this gene revealed sequences homologous to regulatory elements for glucocorticoids, metal ions, and cAMP. The latter is especially significant since recent evidence suggests that the rat BGP gene can be regulated by cAMP. This region of the gene also contains numerous pairs of inverted repeat sequences (imperfect palindromes). The sequence of the rat BGP gene was compared to that of the recently published human BGP gene (Celeste et al., EMBO J. 5, 1885, 1986). The coding regions of these two genes share 77% sequence identity, and several regions of the 5'-flanking sequences are also well conserved. Knowledge of the sequence of the rat BGP gene will allow studies of its regulation by 1,25(OH)2D3, cAMP, and other trans-acting transcriptional factors, and identification of the regulatory sequence elements involved.
从大鼠基因组文库中分离并测序了大鼠骨钙素(BGP,骨钙蛋白)基因。BGP是一种由钙化组织分泌的5.8-kD非胶原蛋白,其表达受1,25-二羟基维生素D3 [1,25(OH)2D3]调控。BGP基因由4个外显子和3个内含子隔开,跨越近1 kb的DNA。该基因的5'-侧翼区域包含真核基因常见的CCAAT和TATAAA元件。对该基因约600 bp的5'-侧翼序列分析发现了与糖皮质激素、金属离子和cAMP调控元件同源的序列。后者尤为重要,因为最近的证据表明大鼠BGP基因可受cAMP调控。该基因的这一区域还包含许多对反向重复序列(不完全回文)。将大鼠BGP基因的序列与最近发表的人类BGP基因(Celeste等人,《欧洲分子生物学组织杂志》5,1885,1986)的序列进行了比较。这两个基因的编码区序列同一性为77%,5'-侧翼序列的几个区域也高度保守。了解大鼠BGP基因的序列将有助于研究其受1,25(OH)2D3、cAMP和其他反式作用转录因子的调控,并鉴定所涉及的调控序列元件。