Involvement of CREB Binding Protein in Expression of Major Histocompatibility Complex Class II Genes via Interaction with the Class II Transactivator

• DOI: 10.1128/mcb.18.11.6777
• Publication Date: 2015-10-10T00:34:14Z
• Authors: Androniki Kretsovali; Theodora Agalioti; Charalambos Spili...; Eleni Tzortzakaki; Menie Merika; Joseph Papamatheakis
• Keywords: Transcriptional Activation; B-Lymphocytes; Genes, MHC Class II; Nuclear Proteins; Cell Line; 3. Good health; Interferon-gamma; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Trans-Activators; Adenovirus E1A Proteins; Cyclic AMP Response Element-Binding Protein; Promoter Regions, Genetic; Protein Binding; Signal Transduction

The class II transactivator (CIITA) is a key regulatory factor that controls expression of the major histocompatibility complex (MHC) class II genes that are essential components for antigen presentation and thus regulation of the immune response. We show here that the adenovirus E1A protein interferes with the action of CIITA and inhibits both B-cell-specific and gamma interferon (IFN-gamma)-induced expression of MHC class II promoters. Transfection studies provide evidence for the functional role of the CREB-binding protein (CBP) in IFN-gamma and CIITA-mediated MHC class II promoter activation. We demonstrate that the N-terminally located transcription activation domain of CIITA physically interacts with both the N-terminal and the E1A-binding (C/H3) regions of CBP. These results suggest the involvement of a multisubunit complex, which contains the gene-specific coactivator CIITA and the versatile coactivator CBP, in MHC class II gene regulation, which may be responsible for both high-level expression and modulation by different signaling pathways.