Human angiotensin II type-1 receptor gene and regulation.

本研究对人血管紧张素Ⅱ 1型受体（AT_1）基因组结构进行了研究。从cDNA中筛选出人AT_1基因的5个外显子和前4个外显子编码5 '端非翻译DNA序列。每个阳性克隆具有不同的外显子，用于构建包括外显子/内含子连接位点的人类AT_1基因图谱。在外显子的所有边界都发现了典型的内含子供体和受体位点。测序结果表明，人AT_1基因5 '端非翻译区由4个外显子组成。如在所有选择性剪接的人AT_1转录物中所见，这些转录物编码相同的受体，表明存在含有第一外显子的单个功能性启动子。对第一外显子上游的基因组DNA序列的分析显示，在各种基因的启动子中揭示了几个序列基序; Sp1具有两种不同类型的GC盒、两个CAAT盒、AP-2.Pit-1（垂体转录激活因子）和白蛋白阴性因子（ANF）。几个顺式作用的调控元件也进行了表征。对5 '侧翼区的功能分析结果表明，该基因的转录有正调控和负调控两种。

Our studies were focused on the determination of the genomic organization of human angiotensin II type-1 receptor (AT_1) gene. The presence of five exons for human AT_1 gene and the first four exons encoding 5'untranslated DNA sequences were found from the screenings of the cDNAs. Each positive clone had different exons that were used to construct the map of human AT_1 gene including exon/intron junction sites. Typical intron donor and acceptor sites were found at all the borders of the exons. Sequencing results suggest that the 5'-untranslated region of human AT_1 gene consists of four exons. As seen in all the alternatively spliced human AT_1 transcripts, those transcripts encode the same and the single receptor suggesting the presence of a single functional promoter which contains the first exon. Analysis of the genomic DNA sequence upstream of the first exon showed several sequence motifs revealed in the promoters of the various genes ; Sp1 with two different types of GC boxes, two CAAT boxes, AP-2.Pit-1 (a pituitary transcriptional activator), and albumin-negative factor (ANF). Several cis-acting regulatory elements were also characterized. The results of functional analysis of the 5'-flanking region suggest positive and negative regulations of the transcription.