Binding of YY1 to the Proximal Region of the Murine Beta Interferon Promoter Is Essential To Allow CBP Recruitment and K8H4/K14H3 Acetylation on the Promoter Region after Virus Infection

Abstract

ABSTRACT Virus-induced activation of the beta interferon (IFN-β) gene requires orderly recruitment of chromatin-remodeling complexes and time-regulated acetylation of histone residues K8H4 and K14H3 on the promoter region. We have previously shown that transcription factor Yin Yang 1 (YY1) binds the murine IFN-β promoter at two sites (−122 and −90) regulating promoter transcriptional capacity with a dual activator/repressor role. In this work we demonstrate that both YY1 −122 and −90 sites are required for CBP recruitment and K8H4/K14H3 acetylation to take place on the IFN-β promoter region after virus infection. A single point mutation introduced at either one of these two sites inhibiting YY1 binding completely disrupted CBP recruitment and K8H4/K14H3 acetylation independently of HMGI or IRF3 binding to the promoter. We have previously demonstrated that YY1 represses the transcriptional capacity of the IFN-β promoter through its −90 site via histone deacetylation. Here we demonstrate that, in vivo, the binding of YY1 to the −90 site is constant all through virus infection whereas the binding of YY1 to the −122 site is activated after infection. We discuss here the capacity of YY1 to either repress (through histone deacetylase recruitment) or activate (through CBP recruitment) IFN-β gene expression according to the occupancy of either only its −90 site or both its −122 and −90 sites.