Transcription Factor YY1 Binds to the Murine Beta Interferon Promoter and Regulates Its Transcriptional Capacity with a Dual Activator/Repressor Role

Abstract

ABSTRACT The induction of the beta interferon (IFN-β) gene constitutes one of the first responses of the cell to virus infection. Its regulation is achieved through an intricate combination of virus-induced binding of transcription factors and local chromatin remodeling. In this work, we demonstrate that transcription factor YY1, known to interact with histone deacetylases (HDAC) and histone acetyltransferases, has a dual activator/repressor role during the regulation of the IFN-β promoter activity. We show that YY1 specifically binds in vitro and in vivo to the murine IFN-β promoter at positions −90 and −122. Overexpression of YY1 strongly repressed the transcriptional capacity of a stably integrated IFN-β promoter fused to a chloramphenicol acetyltransferase reporter gene as well as the endogenous IFN activity of murine L929 cells via an HDAC activity. Stably integrated IFN-β promoters mutated at the −90 site were no longer repressed by YY1, could no longer be activated by trichostatin A, displayed a retarded postinduction turn off, and a reduced virus-induced activity. Introduction of a mutation at the −122 site did not affect YY1-induced repression, but promoters with this mutation displayed a reduced virus-induced activity. Stably integrated full-length promoters (from position −330 to +20) mutated at both YY1-binding sites displayed extremely reduced promoter activities. We conclude that YY1 has a dual activator/repressor role on IFN-β promoter activity depending on its binding site and time after infection.