Molecular variation of the human angiotensinogen core promoter element located between the TATA box and transcription initiation site affects its transcriptional activity.
Recent genetic studies indicate that several molecular variants discovered in angiotensinogen (AG), the precursor of vasoactive octapeptide angiotensin II, could potentially be responsible for inherited predisposition to human blood pressure variation. We have previously shown that a ubiquitously expressed nuclear factor, AGCF1, bound to AGCE1 (AG core promoter element 1 including the core nucleotides, CTCGTG, CTC-type) located between the TATA box and transcription initiation site (positions -25 to -1) is an authentic regulator of human AG transcription. In the present study, we showed that AGCF1 has biologically and immunologically similar properties to those of a helix-loop-helix nuclear factor USF1 and examined the effects of two other naturally occurring molecular variants (ATCGTG, ATC-type and ATTGTG, ATT-type) found in the AGCE1 position on the human AG transcriptional activity. Competitive gel-shift and transfection experiments demonstrated that the transcriptional activity for the CTC- and ATC-type promoters was 2.5 times higher than that for the ATT-type through the alteration of AGCF1-binding affinity. These results suggest the possible involvement of USF1 as a component in AGCF1 formation and the potential importance of AGCE1 variation in blood pressure regulation through human AG expression.
Yanai
K
K
Institute of Applied Biochemistry, Tsukuba, Ibaraki 305, Japan. akif@sakura.cc.tsukuba.ac.jp
Saito
T
T
Hirota
K
K
Kobayashi
H
H
Murakami
K
K
Fukamizu
A
A
D000808:Angiotensinogen / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship; D016385:TATA Box; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; D000808:Angiotensinogen; D004247:DNA