Binding of YY1 to the proximal region of the murine interferon {beta} promoter is essential to allow CBP-recruitment and K8H4/K14H3 acetylation on the promoter region after virus infection.
Résumé
Virus-induced activation of the interferon-beta (IFN-beta) 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 YY1 binds the murine IFN-beta promoter at two sites (-122 and -90) regulating the 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-beta promoter region after virus infection. 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-beta promoter through its -90 site via histone deacetylation. Here we demonstrate that in vivo, binding of YY1 to the -90 site is constant all through virus infection whereas binding of YY1 to the -122 site is activated after infection. We discuss here the capacity of YY1 to either repress (through HDAC recruitment) or activate (through CBP recruitment) IFN-beta gene expression according to the occupancy of either only its -90 site or both its -122 and the -90 sites.