An HLA-B regulatory element binds a factor immunologically related to the upstream stimulation factor.

ABSTRACT

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.