AN HLA-B REGULATORY ELEMENT BINDS A FACTOR IMMUNOLOGICALLY RELATED TOTHE 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 le vels of HLA-A and -B expression can vary, and HLA-B loci are induced m uch more strongly by IFNs. Constitutive activity is dependent on an up stream enhancer (ENH) which contains a rel (KBF, NFkappaB) binding mot if, and induction is mediated by an interferon response element (IRE) which binds members of the IRF family. Reported here is the identifica tion of a regulatory element, 'R', which overlaps the IRE of HLA-B loc i, 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 facto r which is recognized by an antiserum raised against the upstream stim ulation 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 IFNalpha in some cell lin es, which appears to be due to competitive binding of USF with IRF pro teins.