TRANSCRIPTION OF THE RAT ALPHA(1B) ADRENERGIC-RECEPTOR GENE IN LIVER IS CONTROLLED BY 3 PROMOTERS

The proximal 5'-flanking region of the rat alpha(1B) adrenergic recept or (alpha(1B)AR) gene contains discrete transcription start points (ts p) utilized in liver, located at -54, -57 (tsp1), and -443 base pairs (tsp2) upstream from the translation start codon (Gao, B., and Kunos, G. (1993) Gene (Amst.) 131, 243-247). Primer extension analyses using 5' upstream primers now identify an additional cluster of tsp between -1035 and -1340 base pairs (tsp3). Northern blots of rat liver mRNA re veal three alpha(1B)AR mRNAs of 2.3, 2.7, and 3.3 kilobases in length. Transient transfections of putative promoter/pCAT constructs document the existence of three promoters, P1 (-127, -49), P2 (-813, -432), an d P3 (-1363, -1107), which direct transcription from tsp1, tsp2, and t sp3, respectively. P1 contains no recognition sequences for known tran scription factors. P2 is (G + C)-rich, lacks a TATA box, and contains a cAMP response element, GC, CACC, and GCAAT boxes, and binding sites for nuclear factor I. P3 contains a putative TATATA and CCAAT box and is flanked by recognition sites for the liver-specific CCAAT/enhancer binding protein and hepatocyte nuclear factor 5. These findings indica te that heterogeneity of alpha(1B)AR mRNA in liver is related to trans cription of the gene by three distinct promoters. Differential control of these promoters may underlie the well documented developmental and tissue-specific regulation of the alpha(1B)AR.