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Volume 272, Number 48, Issue of November 28, 1997 pp. 30558-30562
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular Variation of the Human Angiotensinogen Core Promoter Element Located between the TATA Box and Transcription Initiation Site Affects Its Transcriptional Activity

(Received for publication, May 14, 1997, and in revised form, August 27, 1997)

Kazuyuki Yanai , Tomoko Saito , Keiko Hirota , Hideyuki Kobayashi ^¶ , Kazuo Murakami and Akiyoshi Fukamizu

From the  Institute of Applied Biochemistry,  Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Molecular Function Laboratory, ^¶ National Food Research Institute, Tsukuba, Ibaraki 305, Japan

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.

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