STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF HUMAN AROMATASE P-450 GENE
STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF HUMAN AROMATASE P-450 GENE
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DOI：
10.1111/j.1432-1033.1990.tb19372.x
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发表时间：
1990-10-24
期刊：
影响因子：
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通讯作者：
SHIZUTA, Y
中科院分区：
文献类型：
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作者：
TODA, K;TERASHIMA, M;SHIZUTA, Y
从两种类型的人类基因组DNA文库中分离到了编码芳香酶P-450(CYP XIX)的基因。该基因全长至少70kb，由10个外显子组成。翻译起始点和终止点分别位于外显子2和外显子10。该基因的启动子区域含有一个TATA盒、一个CAAT盒和两个推测的AP-1结合位点，分别始于转录起始点的-28、-83、-55和-68bp。此外，在-209和-196之间观察到回文核苷酸序列，在-485和-433之间和-358和-331之间的区域中还存在两种类型的重复六核苷酸(一致认为：AATGAA和CCATA[或G]A[或G])。对含有不同长度的氯霉素乙酰转移酶基因5‘-侧翼区的瞬时表达研究表明，在-500和-243之间的区域含有负顺作用元件(S)，而在-242和-183之间的区域是有效转录活性所必需的。Northern印迹分析表明，经12-O-十四酰佛波醇13-乙酸酯处理细胞后，芳香糖P-450基因的表达明显增强。氯霉素乙酰转移酶分析表明，相对于转录起始点的-242位核苷酸区域参与了对佛波酯的转录反应。
The gene encoding aromatase P-450 (CYP XIX) has been isolated from two types of human genomic DNA libraries. It spans at least 70 kb and consists of 10 exons. The translational initiation site and the termination site are located in exon 2 and exon 10, respectively. The promoter region of the gene contains a TATA box, a CAAT box and two putative AP-1 binding sites beginning at -28, -83, -55 and -68 bp, respectively, from the transcriptional initiation site. In addition, a palindromic nucleotide sequence is observed between -209 and -196 and two types of repetitious hexanucleotide (consensus: AATGAA and CCATA[or G]A[or G]) are also present within the regions between -485 and -433 and between -358 and -331. Transient expression studies of chloramphenicol acetyltransferase constructs bearing various lengths of 5''-flanking region of the gene show that the region between -500 and -243 contains negative cis-acting element(s), whereas the region between -242 and -183 is required for efficient transcriptional activity. Northern blot analysis demonstrates that the expression of aromatose P-450 gene is remarkably stimulated by treatment of cells with 12-O-tetradecanoyl-phorbol 13-acetate. By chloramphenicol acetyltransferase assay the region up to nucleotide position -242 relative to the transcriptional initiation site is shown to participate in the transcriptional responsiveness to this phorbol ester.