Interactions between the Class II Transactivator and CREB Binding Protein Increase Transcription of Major Histocompatibility Complex Class II Genes

Abstract

Class II major histocompatibility (class II) genes are regulated in a B-cell-specific and gamma interferon-inducible fashion. The master switch for the 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 the CREB binding protein (CBP) to class II promoters. Not only functional but also specific binding interactions between CIITA and CBP were 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 hormone could be attributed to the squelching of CBP by the glucocorticoid receptor. We conclude that CBP, a histone acetyltransferase, plays an important role in the transcription of class II genes.

ACKNOWLEDGMENTS

We thank Michael Armanini for expert secretarial assistance, members of the Peterlin lab and Peter Kushner for helpful comments and discussions, and G. M. Rosenfeld for pCMVCBP.

This work was supported by a postdoctoral fellowship grant from the Arthritis Foundation to J.D.F. and a grant from the Nora Eccles Treadwell Foundation to B.M.P.