Two DNA-binding proteins discriminate between the promoters of different members of the major histocompatibility complex class II multigene family.
The regulation of major histocompatibility complex (MHC) class II gene expression is a key feature of the control of normal and abnormal immune responses. In humans, class II alpha - and beta-chain genes are organized in a multigene family with three distinct subregions, HLA-DR, -DQ, and -DP. The regulation of these genes is generally coordinated, and their promoters contain highly conserved motifs, in particular the X and Y boxes. We have identified five distinct proteins that bind to specific DNA sequences within the first 145 base pairs of the HLA-DR promoter, a segment known to be functionally essential for class II gene regulation. Among these, RF-X is of special interest, since mutants affected in the regulation of MHC class II gene expression have a specific defect in RF-X binding. Unexpectedly, RF-X displays a characteristic gradient of binding affinities for the X boxes of three alpha-chain genes (DRA greater than DPA much greater than DQA). The same observation was made with recombinant RF-X. We also describe a novel factor, NF-S, which bound to the spacer region between the X and Y boxes of class II promoters. NF-S exhibited a reverse gradient of affinity compared with RF-X (DQA greater than DPA much greater than DRA). As expected, RF-X bound well to the mouse IE alpha promoter, while NF-S bound well to IA alpha. The drastic differences in the binding of RF-X and NF-S to different MHC class II promoters contrasts with the coordinate regulation of HLA-DR, -DQ, and -DP genes.
Kobr
M
M
Department of Microbiology, University of Geneva Medical School, Switzerland.
Reith
W
W
Herrero-Sanchez
C
C
Mach
B
B
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; D014157:Transcription Factors