Identification of two distinct Sp1- and RBF-1-like nuclear factors that bind to the upstream region of the human angiotensinogen promoter

Abstract

Angiotensionogen, the protein precursor of angiotensin II that is a crucial regulator of blood pressure and electrolyte balance, is constitutively produced by the liver. In the present study, we identified two nuclear factors that are possibly involved in maintaining the constitutive promoter activity of the human angiotensinogen gene. The 32 bp DNA region between -344 and -313 located in the 1.3 kb angiotensinogen upstream region (-1222 to +44) partially contributed to the maintenance of the efficient promoter activity in HepG2 cells. This segment was able to form the complexes with HepG2 nuclear extracts, which could be dissociated by competing recognition sequences that contain those of either Sp1 or RBF-1. Anin vivo competition experiment demonstrated that the parental promoter activity is reduced about 65% by an RBF-1 competitor more effectively than by an Sp1 competitor. These results suggested that Sp1- and RBF-1-like factors play roles in maintaining the constitutively active angiotensinogen promoter.