Regulated expression of human angiotensinogen gene by hepatocyte nuclear factor 4 and chicken ovalbumin upstream promoter-transcription factor

We previously identified various upstream and downstream regulatory element s and factors important for hepatic expression of the human angiotensinogen (ANG) gene, the precursor of vasoactive octapeptide angiotensin II. In the present study, to further investigate the molecular mechanism of human ANG transcriptional regulation, we generated transgenic mice carrying the fusi on gene composed of the 1.3-kilobase promoter of the human ANG gene, its do wnstream enhancer, and the chloramphenicol acetyltransferase reporter gene. Because expression of the chloramphenicol acetyltransferase gene was obser ved strongly in the liver and weakly in the kidney, we suspected that hepat ocyte nuclear factor (HNF) 4 with a tissue expression pattern similar to th at of the reporter gene would regulate ANG transcription. In vitro assays i ndicated that HNF4 bound to the promoter elements and strongly activated th e ANG transcription, but that chicken ovalbumin upstream promoter transcrip tion factor (COUP-TF), a transcriptional repressor, dramatically repressed human ANG transcription through the promoter elements and the downstream en hancer core elements. Furthermore, COUP-TF dramatically decreased the human ANG transcription in the mouse liver by the Hellos Gene Gun system in vivo , These results suggest that an interplay between HNF4 and COUP-TF could be important in hepatic human ANG transcription.