K. Yanai et al., Regulated expression of human angiotensinogen gene by hepatocyte nuclear factor 4 and chicken ovalbumin upstream promoter-transcription factor, J BIOL CHEM, 274(49), 1999, pp. 34605-34612
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.