Interactions between the class II transactivator and CREB binding protein increase transcription of major histocompatibility complex class II genes

Class II major histocompatibility (class II) genes are regulated in a B-cel l-specific and gamma interferon-inducible fashion. The master switch for th e expression of these genes is the class II transactivator (CIITA). In this report, we demonstrate that one of the functions of CIITA is to recruit th e CREB binding protein (CBP) to class II promoters. Not only functional but also specific binding interactions between CIITA and CBP mere demonstrated . Moreover, a dominant negative form of CBP decreased the activity of class II promoters and levels of class II determinants on the surface of cells. Finally, the inhibition of class II gene expression by the glucocorticoid h ormone could be attributed to the squelching of CBP by the glucocorticoid r eceptor. We conclude that CBP, a histone acetyltransferase, plays an import ant role in the transcription of class II genes.