CIITA-induced occupation of MHC class II promoters is independent of the cooperative stabilization of the promoter-bound multiprotein complexes

Precise regulation of MHC class II expression plays a crucial role in the c ontrol of the immune response. The transactivator CIITA behaves as a master controller of constitutive and inducible MHC class Ii gene activation, but its exact mechanism of action is not known. Activation of MHC class II pro moters requires binding of at least three distinct multi-protein complexes (RFX, X2BP and NF-Y). It is known that the stability of this binding result s from cooperative interactions between these proteins. We show here that e xpression of CIITA in MHC class II- cells triggers occupation of the promot ers by these complexes. This observation raised the possibility that the ef fect of CIITA on promoter occupation is mediated by an effect on the cooper ative stabilization of the DNA-bound multi-protein complexes. We show, howe ver, that the presence of CIITA does not affect the stability of the higher -order protein complex formed on DNA by RFX, X2BP and NF-Y, This suggests o ther mechanisms for CIITA-induced promoter occupancy, such as an effect on chromatin structure leading to increased accessibility of MHC class II prom oters. This ability of CIITA to facilitate promoter occupation is undissoci able from its transactivation potential. Finally, we conclude that this eff ect of CIITA is cell-type specific, since expression of CIITA is not requir ed for normal occupation of MHC class II promoters in a lymphocytes.