An HLA-B regulatory element binds a factor immunologically related to the upstream stimulation factor.
HLA-A and -B are expressed by most cell types, and their levels can be increased by treatment with interferons (IFNs). The relative basal levels of HLA-A and -B expression can vary, and HLA-B loci are induced much more strongly by IFNs. Constitutive activity is dependent on an upstream enhancer (ENH) which contains a rel (KBF, NF kappa B) binding motif, and induction is mediated by an interferon response element (IRE) which binds members of the IRF family. Reported here is the identification of a regulatory element, 'R', which overlaps the IRE of HLA-B loci, but which is absent from the equivalent region of HLA-A or H2 class I genes. The core of the element, CACGAG, is bound by a nuclear factor which is recognized by an antiserum raised against the upstream stimulation factor (USF), a member of the helix-loop-helix/leucine zipper family. The use of reporter gene constructs shows that mutation of the R element results in increased induction by IFN alpha in some cell lines, which appears to be due to competitive binding of USF with IRF proteins.
Girdlestone
J
J
MRC Laboratory of Molecular Biology, MRC Centre, Cambridge, UK.
D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005805:Genes, MHC Class I / Q000235:genetics*; D017930:Genes, Reporter; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014162:Transfection
D004268:DNA-Binding Proteins; D015235:HLA-B Antigens; D007372:Interferons; D015500:Chloramphenicol O-Acetyltransferase