Multiple potential regulatory elements in the 5′ flanking region of the human α1a-adrenergic receptor

In spite of their critical importance in myocardial hypertrophy and benign prostatic hyperplasia, nothing is known about mechanisms underlying transcriptional regulation of alpha(1a)-adrenergic receptors (alpha(1a),ARs). Therefore we cloned 6.2kb of novel sequence upstream of the initiator ATG in the human alpha(1a)AR gene. Sequence analysis reveals a TATA-less promoter, the presence of several initiator (Inr) consensus sequences, multiple GC rich regions consistent with Sp-l binding, and consensus sequences for AP-1 and AP-2 as well. as putative cis transcriptional regulatory elements for binding of CREB (cyclic-AMP response element binding protein), glucocorticoids, estrogen, and insulin. Compared to the alpha(1b)AR, the alpha(1a)LR has several more cis regulatory elements, suggesting more complex regulation. The importance of alpha(1a)ARs in human disease makes it imperative to determine mechanisms underlying transcription and ultimately expression of this receptor. These studies can now be undertaken with the availability of human alpha(1a)AR 5'-flanking and 5'-untranslated sequence.