ヒロタ　ケイコ   Keiko HIROTA   廣田　恵子    所属   医学部 医学科    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Regulated expression of human angiotensinogen gene by hepatocyte nuclear factor 4 and chicken ovalbumin upstream promoter-transcription factor.
掲載誌名	正式名：The Journal of biological chemistry 略　 称：J Biol Chem ISSNコード：00219258/1083351X
掲載区分	国外
巻・号・頁	274(49),pp.34605-34612
著者・共著者	YANAI Kazuyuki†, HIROTA Keiko†, TANIGUCHI Keiko, ARAKAWA Mayumi, NIBU yutaka, SUGIYAMA Fumihiro, YAGAMI Ken-ichi, FUKAMIZU Akiyoshi*
担当区分	筆頭著者
発行年月	1999/12
概要	We previously identified various upstream and downstream regulatory elements 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 fusion gene composed of the 1. 3-kilobase promoter of the human ANG gene, its downstream enhancer, and the chloramphenicol acetyltransferase reporter gene. Because expression of the chloramphenicol acetyltransferase gene was observed strongly in the liver and weakly in the kidney, we suspected that hepatocyte nuclear factor (HNF) 4 with a tissue expression pattern similar to that of the reporter gene would regulate ANG transcription. In vitro assays indicated that HNF4 bound to the promoter elements and strongly activated the ANG transcription, but that chicken ovalbumin upstream promoter transcription factor (COUP-TF), a transcriptional repressor, dramatically repressed human ANG transcription through the promoter elements and the downstream enhancer core elements. Furthermore, COUP-TF dramatically decreased the human ANG transcription in the mouse liver by the Helios Gene Gun system in vivo. These results suggest that an interplay between HNF4 and COUP-TF could be important in hepatic human ANG transcription.