Abstract-Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive hormones, angiotensin II.Human angiotensinogen gene contains a C/A polymorphism at Ϫ20 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at Ϫ20, this sequence binds to the estrogen receptor.We also show that transcriptional activity of reporter constructs containing human angiotensinogen gene promoter with nucleoside A at Ϫ20 is increased on cotransfection of an expression vector containing human estrogen receptor-␣ coding sequence in human hepatoma cells (HepG2) followed by estrogen treatment. On the other hand, adenoviral major late transcription factor binds preferentially to this region of the promoter when nucleoside C is present at Ϫ20. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at Ϫ20 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at Ϫ20. Our data suggest that C/A polymorphism at Ϫ20 may modulate the expression of human angiotensinogen gene in a sex-specific manner. (Hypertension. 1999;33:108-115.)Key Words: angiotensinogen Ⅲ genes Ⅲ polymorphism Ⅲ estrogen Ⅲ gene regulation Ⅲ regulation, hormonal Ⅲ major late transcription factor T he renin-angiotensin system plays an important role in the regulation of blood pressure, fluid balance, and electrolyte homeostasis. Angiotensin II, which is 1 of the most potent vasoactive hormones, is obtained from its precursor molecule, angiotensinogen, by the combined proteolytic action of renin and angiotensin-converting enzyme. Angiotensinogen is primarily synthesized in the liver, although recent studies have shown that its mRNA is also present in fat, brain, kidney, heart, and aorta of rats 1 and humans.2 Because plasma concentration of angiotensinogen is close to the Michaelis constant of the enzymatic reaction between renin and angiotensinogen, 3 a rise or fall in plasma angiotensinogen levels can lead to a parallel change in the formation of angiotensin II, and an increase in plasma angiotensin II may lead to hypertension. Previous studies have shown a highly significant correlation between plasma concentrations of angiotensinogen and blood pressure, 4 higher plasma angiotensinogen concentrations in hypertensive parents and their offspring, 5 and elevations of blood pressure in transgenic animals overexpressing the angiotensinogen gene. 6,7 Recent studies have suggested that the angiotensinogen gene locus is involved in human essential hypertension 8 and pregnancy-induced hypertension.
9Human angiotensinogen gene contains a C/A polymorphism at Ϫ20 located between the TATA box and transcriptional initiation site. 8 We show here that this region of the promoter binds to estrogen receptor-␣ when nucleoside A is present at Ϫ20. We also show that a reporter construct, pHAG1.2CAT (Ϫ20A), is transactivated by cotransfection of the mammalian expression vector pSG5 containing th...
The network consisting of three kinds of unlabeled stem-loop DNA molecular beacons (MBs) is activated by target DNA in the presence of exonuclease-III (Exo-III), achieving the concept of exonuclease-assisted cascaded recycling amplification (Exo-CRA) for DNA detection with a wide dynamic range of 8 orders of magnitude.
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