Soluble guanylyl cyclase (sGC) is the only known receptor for nitric oxide (NO) and is downregulated in aging and hypertension. Little is known about sGC gene transcriptional regulation. In order to characterize the sGC transcriptional system, we cloned and sequenced the 5' flanking region of mouse sGC a(1) gene (AY116663). Structurally, it is a non-canonical TATA-less promoter that we mapped to chromosome 3 with many putative regulation sites for Sp-1, NF-kappaB, and AP-1 transcription factors amongst others, and two (TG:CA)(n) dinucleotide microsatellites near the transcriptional start point. The cloned upstream sequence produced a 5-fold increase in luciferase activity in Cos7, HeLa, NIH3T3, and 293 cells as well as in mouse VSMC-like kidney mesangial cells. In the latter cell type, we showed that sGC alpha(1) promoter activity was dependent on the presence of its 5' unstranslated region (5'UTR). (C) 2003 Elsevier Inc. All rights reserved.