Identification of Yin Yang 1-interacting partners at-1026C/A in the human iNOS promoter

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. (c) 2010 Elsevier Inc. All rights reserved.