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 deficient in certain MHC class II-deficient immunodeficiency patients (CID), and the Y box-binding protein NF-Y bind cooperatively. Functional relevance of this protein-protein interaction is suggested by the fact that promoter activity correlates with cooperative binding of RFX and NF-Y rather 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 results are consistent with the fact that MHC class II promoter function is dependent on correct stereospecific alignment of the X and Y boxes. Cooperative binding involving RFX, NF-Y, and perhaps other MHC class II promoter-binding proteins may 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.
Reith
W
W
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Siegrist
C A
CA
Durand
B
B
Barras
E
E
Mach
B
B
D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005802:Genes, MHC Class II; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D004247:DNA