Human angiotensin II type-1 receptor gene and regulation.

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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.