Previously we demonstrated the association between human iNOS −1026C/A variant and susceptibility to hypertension, and found that −1026C/A altered the Yin Yang 1 (YY1)-binding pattern. In the current study, we verified that −1026C/A was located in a vital regulatory region of the iNOS promoter, wherein existed a DNA-binding complex composed of YY1, nuclear factor I (NFI) and activator protein-1 (AP-1). We also observed that YY1 bound dominantly to −1026C, and NFI bound dominantly to −1026A. Furthermore, the repressive effect of YY1 was more evident than NFI on the iNOS promoter activity, resulting in a more marked reduction of iNOS expression via YY1/AP-1 than via NFI/AP-1 under th... More
Previously we demonstrated the association between human iNOS −1026C/A variant and susceptibility to hypertension, and found that −1026C/A altered the Yin Yang 1 (YY1)-binding pattern. In the current study, we verified that −1026C/A was located in a vital regulatory region of the iNOS promoter, wherein existed a DNA-binding complex composed of YY1, nuclear factor I (NFI) and activator protein-1 (AP-1). We also observed that YY1 bound dominantly to −1026C, and NFI bound dominantly to −1026A. Furthermore, the repressive effect of YY1 was more evident than NFI on the iNOS promoter activity, resulting in a more marked reduction of iNOS expression via YY1/AP-1 than via NFI/AP-1 under the stimulation of cytomix. In conclusion, diverse binding affinities of YY1 and its interacting partners to iNOS −1026C/A resulted in differential promoter activity, and potent inhibition of iNOS expression by YY1/AP-1 complex with −1026C may contribute to an enhanced risk for hypertension.
