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

The mechanism by which IFN-gamma up-regulates invariant chain mRNA in antig en-presenting cells has been under intensive investigation. This study show s that in murine monocytic cells the transcriptional up-regulation mediated by the invariant chain (li) upstream enhancer only accounts for part of th e induction of Ii mRNA by IFN-gamma. We have identified an intronic region in the murine ii gene that contributes to the transcriptional up-regulation by IFN-gamma. The region has S (H), X/X2 and Y boxes similar to those in M HC class II promoters and the ii upstream enhancer. Mutations at the putati ve S, X and Y boxes have abolished the ability of the region to mediate ii up-regulation by IFN-gamma. Consistent with the functions of these boxes, o ur findings reveal that the up-regulation of ii transcription by IFN-gamma mediated by the intronic region is dependent on the induction of class II t ransactivator by IFN-gamma.