FUNCTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II PROMOTERS REQUIRES COOPERATIVE BINDING BETWEEN FACTORS RFX AND NF-Y

Transcription of major histocompatibility complex (MHC) class II genes is controlled largely by the conserved promoter elements called the X and Y boxes. We show here that RFX, the X box binding protein deficie nt in certain MHC class II-deficient immunodeficiency patients (CID), and the Y box-binding protein NF-Y bind cooperatively. Functional rele vance of this protein-protein interaction is suggested by the fact tha t promoter activity correlates with cooperative binding of RFX and NF- Y father than with binding of RFX or NF-Y alone. Stability of the RFX/ NF-Y complex is affected by alterations in X-Y box spacing. These resu lts are consistent with the fact that MHC class II promoter function i s dependent on correct stereospecific alignment of the X and Y boxes. Cooperative binding involving RFX, NF-Y, and perhaps other MHC class I I promoter-binding proteins mag explain why the highly specific defect in binding of RFX observed in CID cells is associated in vivo with a bare promoter in which all of the cis-acting elements, including the X and Y boxes, are unoccupied.