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编码人芳香化酶细胞色素P-450的基因的结构分析,该酶负责雌激素的生物合成。

Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis.

作者信息

Means G D, Mahendroo M S, Corbin C J, Mathis J M, Powell F E, Mendelson C R, Simpson E R

机构信息

Department of Obstetrics and Gynecology, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9051.

出版信息

J Biol Chem. 1989 Nov 15;264(32):19385-91.

PMID:2808431
Abstract

The structural gene encoding aromatase cytochrome P-450 (P-450AROM) was isolated from human genomic DNA. The gene spans at least 52 kilobases and is composed of 10 exons, the first of which is untranslated. Analysis of the transcription initiation site of human P-450AROM mRNA reveals the differential use of 1 of 3 consecutive G residues at the cap site. DNA sequence analysis indicates that the gene has a putative TATA (ATAAAA) sequence at -23 base pairs (bp) and putative CAAT binding sequences beginning at -41, -67, and -83 bp. The 5'-flanking region contains sequences similar to consensus sequences of cis-acting elements defined as regulators of aromatase gene expression. These putative sequences include a cAMP regulatory element at -211 bp, an AP1 (protein kinase C) site at -54 bp, and glucocorticoid regulatory elements at -352 bp and within the first intron at +346 bp. There appears to be only one gene encoding P-450AROM in the human genome. Two major species of human P-450AROM mRNA (3.4 and 2.9 kilobases) are derived from the use of two polyadenylation signals.

摘要

编码芳香化酶细胞色素P-450(P-450AROM)的结构基因是从人类基因组DNA中分离出来的。该基因跨度至少52千碱基,由10个外显子组成,其中第一个外显子是未翻译的。对人类P-450AROM mRNA转录起始位点的分析揭示了在帽位点3个连续G残基中1个的差异使用情况。DNA序列分析表明,该基因在-23个碱基对(bp)处有一个推定的TATA(ATAAAA)序列,在-41、-67和-83 bp处开始有推定的CAAT结合序列。5'侧翼区域包含与被定义为芳香化酶基因表达调节因子的顺式作用元件共有序列相似的序列。这些推定序列包括-211 bp处的一个cAMP调节元件、-54 bp处的一个AP1(蛋白激酶C)位点以及-352 bp处和第一个内含子中+346 bp处的糖皮质激素调节元件。在人类基因组中似乎只有一个编码P-450AROM的基因。两种主要的人类P-450AROM mRNA(3.4和2.9千碱基)来自于两个聚腺苷酸化信号的使用。

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