THE NUCLEAR FACTOR YY1 SUPPRESSES THE HUMAN GAMMA-INTERFERON PROMOTERTHROUGH 2 MECHANISMS - INHIBITION OF AP1 BINDING AND ACTIVATION OF A SILENCER ELEMENT

Our group has previously reported that the nuclear factor Yin-Yang 1 ( YY1), a ubiquitous DNA-binding protein, is able to interact with a sil encer element (BE) in the gamma interferon (IFN-gamma) promoter region , In this study, we demonstrated that YY1 can directly inhibit the act ivity of the IFN-gamma promoter by interacting with multiple sites in the promoter, In cotransfection assays, a YY1 expression vector signif icantly inhibited IFN-gamma promoter activity, Mutation of the YY1 bin ding site in the native IFN-gamma promoter was associated with an incr ease in the IFN-gamma promoter activity, Analysis of the DNA sequences of the IFN-gamma promoter revealed a second functional YY1 binding si te (BED) that overlaps with an AP1 binding site. In this element, AP1 enhancer activity was suppressed by YY1. Since the nuclear level of YY 1 does not change upon cell activation, our data support a model that the nuclear factor YY1 acts to suppress basal IFN-gamma transcription by interacting with the promoter at multiple DNA binding sites, This r epression can occur through two mechanisms: (i) cooperation with an as -yet-unidentified AP2-like repressor protein and (ii) competition for DNA binding,vith the transactivating factor AP1.