Identification of an IFN-γ responsive region in an intron of the invariant chain gene

Abstract

The mechanism by which IFN-γ up-regulates invariant chain mRNA in antigen-presenting cells has been under intensive investigation. This study shows that in murine monocytic cells the transcriptional up-regulation mediated by the invariant chain (li) upstream enhancer only accounts for part of the induction of li mRNA by IFN-γ. We have identified an intronic region in the murine li gene that contributes to the transcriptional up-regulation by IFN-γ. The region has S (H), X/X2 and Y boxes similar to those in MHC class II promoters and the li upstream enhancer. Mutations at the putative S, X and Y boxes have abolished the ability of the region to mediate li up-regulation by IFN-γ. Consistent with the functions of these boxes, our findings reveal that the up-regulation of li transcription by IFN-γ mediated by the intronic region is dependent on the induction of class II transactivator by IFN-γ.