Transcriptional regulation of HLA-A and -B: differential binding of members of the Rel and IRF families of transcription factors.
HLA-A and -B transplantation antigens can be expressed differentially at the basal level and in response to interferons (IFNs). To determine which DNA control elements and nuclear factors are responsible for these differences, HLA-A and -B upstream regulatory regions were used in expression and mobility-shift analyses. The HLA-A enhancer was found to contain two Rel (KBF/NF-kappa B) binding motifs, while the HLA-B enhancer has only one and is transactivated less well by overexpression of the NF-kappa B p65 subunit. On the other hand, the HLA-B IFN response element mediates a much stronger induction by IFNs and has a higher affinity for IRF-1 and -2, which are transcription factors implicated in the regulation of major histocompatibility complex class I genes. These results suggest a molecular basis for the way in which HLA-A and -B loci have adapted to be differentially expressed and to respond to different sets of cytokine signals.
Girdlestone
J
J
Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge, United Kingdom.
Isamat
M
M
Gewert
D
D
Milstein
C
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D015234:HLA-A Antigens / Q000096:biosynthesis*; D015235:HLA-B Antigens / Q000096:biosynthesis*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007700:Kinetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D010750:Phosphoproteins / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D015235:HLA-B Antigens; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors