Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) Type IV promoter by interferon regulatory factors 1 and 2

Class II transactivator (CIITA) activates the expression of major histocomp atibility class II genes, which encode antigen-presenting molecules recogni zed by the T-cell receptor of CD4+ T cells. IFN-gamma induced CIITA transcr iption in many cell types is directed by the CIITA Type IV promoter. Here w e report that the human CIITA Type IV promoter TRF-E binds IRF-1 and can be activated by exogenous expression of IRF-1. Surprisingly, the CIITA Type I V promoter IRF-E is also activated by IRF-2, another member of the IRF fami ly that generally acts as a transcriptional repressor. In addition, we foun d that IRF-1 and IRF-2 synergistically activate the CIITA Type IV promoter. Electrophoretic mobility shift assays revealed that IRF-1 and IRF-2 can si multaneously occupy the IRF-E of the CIITA Type IV promoter, suggesting a n ovel mechanism for the role of these two proteins in promoter activation. O ur results also indicate that IRF-1 and IRF-2 can cooperatively activate an d co-occupy the IRF-E of the guanylate binding protein (GBP) promoter. Fina lly, CIITA induction by IFN-gamma does not occur in a pancreatic tumor cell line that expresses a mutated IRF-2, representing the first IRF-2 mutation identified in a human tumor cell line.