ATF-like element contributes to hepatic activation of human angiotensinogen promoter

Angiotensinogen is the precursor protein of angiotensin II that is involved in regulating blood pressure and electrolyte homeostasis, and it is mainly synthesized in the liver. In the present study, we analyzed the human angiotensinogen proximal promoter region by means of Chloramphenicol acetyltransferase assays, and suggested that the region from -106 to +44 is sufficient for hepatoma cell line (HepG2)-specific expression. Electrophoretic mobility shift assays using ALE (ATF-like element, -102 to -87) fragment identified CREB/ATF family nuclear factors and novel ones, ALF (ALE-binding factor). The deletion and in vivo competition of ALE decreased the human angiotensinogen promoter activity. Furthermore, the heterologous promoter analysis demonstrated that ALE acts as a HepG2-dependent activating element. These results indicate that ALE plays an important role in hepatic expression of human angiotensinogen gene.