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.
Li
Wei
W
Department of Medical Genetics, China Medical University, No. 92 Bei Er Road, Shenyang, China.
Liu
Hong
H
Fu
Lingyu
L
Li
Dejun
D
Zhao
Yanyan
Y
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D056945:Hep G2 Cells; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020218:Response Elements; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D050986:YY1 Transcription Factor
D046912:Multiprotein Complexes; D051839:NFI Transcription Factors; D018808:Transcription Factor AP-1; D050986:YY1 Transcription Factor; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II