COMPLEX ARCHITECTURE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II PROMOTERS - REITERATED MOTIFS AND CONSERVED PROTEIN-PROTEIN INTERACTIONS

The S box (also known as at the H, W, or Z box) is the 5'-most element of the conserved upstream sequences in promoters of major histocompat ibility complex class II genes. It is important for their B-cell-speci fic and interferon gamma-inducible expression. In this study, we demon strate that the S box represents a duplication of the downstream X box . First, RFX, which is composed of the RFX5-p36 heterodimer that binds to the X box, also binds to the S box and its 5'-flanking sequence. S econd, NF-Y, which binds to the Y box and increases interactions betwe en RFX and the X box, also increases the binding of RFX to the S box. Third, RFXs bound to S and X boxes interact with each other in a spati ally constrained manner. Finally, rye confirmed these protein-protein and protein-DNA interactions by expressing a hybrid RFX5-VP16 protein in cells. We conclude that RFX binds to S and X boxes and that complex interactions between RFX and NF-Y direct B-cell-specific and interfer on gamma-inducible expression of major histocompatibility complex clas s II genes.