SITE-ALPHA IS CRUCIAL FOR 2 ROUTES OF IFN-GAMMA-INDUCED MHC CLASS-I TRANSACTIVATION - THE ISRE-MEDIATED ROUTE AND A NOVEL PATHWAY INVOLVINGCIITA

The constitutive and cytokine-induced levels of major histocompatibili ty (MHC) class I expression are tightly controlled at the transcriptio nal level. In this study, it is shown that the cis-acting regulatory e lement site alpha of the MHC class I promoter is essential for the IFN gamma-induced transactivation of MHC class I gene expression through the ISRE. Moreover, it was discovered that the class II transactivator (CIITA), which is itself under the control of the IFN gamma induction pathway, strongly transactivates MHC class I gene expression and exer ts its activity through site alpha. Therefore, site alpha is a crucial regulatory element, mediating the classic route of IFN gamma inductio n via the ISRE as well as a novel route of MHC class I transactivation involving CIITA.