CREB regulates MHC class II expression in a CIITA-dependent manner

The X2 box of MHC class II promoters is homologous to TRE/CRE elements and is required for expression of MHC class II genes. The X2 box-specific DNA b inding activity, X2BP, was purified to homogeneity, sequenced, and identifi ed as CREB. Transient transactivation experiments showed that CREB can coop erate with CIITA to enhance activation of transcription from MHC class II p romoters in a dose-dependent manner. Binding of CREB to the class II promot er in vivo was demonstrated by a chromatin immunoprecipitation assay. Addit ionally, ICER, a dominant inhibitor of CREB function, was found to repress class II expression. These results demonstrate that CREB binds to the X2 bo x in vivo and cooperates with CIITA to direct MHC class II expression.