COOPERATIVE BINDING BETWEEN FACTOR-RFX AND FACTOR-X2BP TO THE X-BOX AND X2-BOX OF MHC CLASS-II PROMOTERS

Transcription of major histocompatibility complex (MHC) class II genes is controlled primarily by the promoter, which contains several conse rved cis-acting elements, including the X, X2, and Y boxes. We show he re that RFX, the X box-binding protein that is deficient in certain MH C class II regulatory mutants, binds cooperatively with an X2 box-bind ing protein (X2bp) to form an RFX.X2bp.DNA complex in which the intera ction of the two factors with their target sites is strongly stabilize d. A functional role of this RFX.X2bp complex is consistent with mutat ional analysis of the X and X2 boxes of the DRA and DRB1 class II prom oters. Together with previous results demonstrating cooperative bindin g between RFX and the Y box-binding protein NF-Y, our results indicate that RFX plays a central role in promoting cooperative binding intera ctions required for stable occupation of the MHC class II promoter. Th is may explain why the highly specific defect in binding of RFX observ ed in certain MHC class II regulatory mutants is associated in vivo wi th a bare promoter in which all of the cis-acting elements, including the X, X2, and Y boxes, are unoccupied.