THE ROLE OF ENHANCER-A IN THE LOCUS-SPECIFIC TRANSACTIVATION OF CLASSICAL AND NONCLASSICAL HLA CLASS-I GENES BY NUCLEAR FACTOR KAPPA-B

HLA class I expression is tightly controlled at the transcriptional le vel by several conserved regulatory elements in the proximal promoter region. In this study, the two putative kappa B motifs of enhancer A ( kappa B1 and kappa B2) of the classical and nonclassical HLA class I g enes were investigated for their binding properties of transcription f actors and tested for their contribution to the NF-kappa B-induced rou te of transactivation. It was shown that NF-kappa B-induced transactiv ation through enhancer A is most important for the HLA-A locus, which contains two NF-kappa B binding sites. Although the enhancer A of HLA- B contains only one NF-kappa B binding site (kappa B1), there was stil l a moderate transactivation by NF-kappa B. Since HLA-F, which also po ssesses one NF-kappa B binding site but lacks protein binding to its k appa B2 site, was not transactivated by NF-kappa B, the NF-kappa B-med iated transactivation through the kappa B1 motif in HLA-B is most prob ably facilitated by binding of the transcription factor Sp1 to the ups tream kappa B2 site. Thus, transcriptional regulation of HLA class I g enes by NF-kappa B is restricted to the HLA-A and HLA-B loci.