A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen α₂(I) and Other Promoters

Abstract

The class II transactivator (CIITA) is induced by gamma interferon (IFN-γ) and activates major histocompatibility complex class II; however, this report shows it suppresses other genes. An N-terminal 36 amino acids of CIITA mediates suppression of the collagen α₂(I) promoter via binding to CREB-binding protein (CBP). Reconstitution of cells with CBP reverts this suppression. IFN-γ is known to inhibit collagen gene expression; to test if CIITA mediates this gene suppression, a mutant cell line defective in CIITA induction but not in the activation of STAT1/JAK/IRF-1 is studied. IFN-γ suppression of the collagen promoter and the endogenous gene is observed in the wild-type control but not in the mutant line. Suppression is restored when CIITA is introduced. Other targets of CIITA-mediated promoter suppression include interleukin 4, thymidine kinase, and cyclin D1.

ACKNOWLEDGMENTS

We thank M. Li-Weber for IL-4–CAT and TK-CAT, Albert Baldwin for CD-Luc, and R. H. Goodman for CMV5-CBP.

This study was supported by grants from the National Institutes of Health (AI45580, AI41751, AI29565, and DK38108 to J.P.-Y.T.) and the National Multiple Sclerosis Society (RG7815 to J.P.-Y.T.).