Contribution of Sp1 to initiation of transcription of angiotensinogen.
Several genetic polymorphisms have been identified in the proximal promoter of angiotensinogen ( AGT). Gene titration experiments in transgenic animals have demonstrated that small increases in the basal expression of AGT can lead to elevated blood pressure. The direct proof that promoter variants of AGT can lead to elevated blood pressure will ultimately require the development of specific animal models. Before such work can be contemplated, however, a formal understanding of the mechanisms controlling transcriptional activation of AGT needs to be developed. Analysis of DNA-protein interactions in vitro and transactivation experiments in cultured cells reveal the critical role of an Sp1 binding site immediately upstream of the TATA box of AGT in both mouse and human. Both sites are required for transcription initiation in the mouse. By contrast, a minimal human AGT promoter can initiate transcription in the absence of either this Sp1 site or the TATA box, albeit at a lower level. Further analysis and consideration of these interspecific differences will be essential for the development of meaningful animal models to probe the mechanism by which AGT may predispose to human essential hypertension.
Rohrwasser
Andreas
A
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Zhang
Shuhua
S
Dillon
Harrison F
HF
Inoue
Ituro
I
Callaway
Christopher W
CW
Hillas
Elaine
E
Lalouel
Jean-Marc
JM
D000808:Angiotensinogen / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D018983:DNA Footprinting; D017931:DNA Primers / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016329:Sp1 Transcription Factor; D000808:Angiotensinogen; D008156:Luciferases; D003850:Deoxyribonuclease I