The role of enhancer A in the locus-specific transactivation of classical and nonclassical HLA class I genes by nuclear factor kappa B

Abstract

HLA class I expression is tightly controlled at the transcriptional level 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 genes were investigated for their binding properties of transcription factors and tested for their contribution to the NF-kappa B-induced route of transactivation. It was shown that NF-kappa B-induced transactivation 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 still a moderate transactivation by NF-kappa B. Since HLA-F, which also possesses one NF-kappa B binding site but lacks protein binding to its KB2 site, was not transactivated by NF-kappa B, the NF-kappa B-mediated transactivation through the kappa B1 motif in HLA-B is most probably facilitated by binding of the transcription factor Spl to the upstream kappa B2 site. Thus, transcriptional regulation of HLA class I genes by NF-kappa B is restricted to the HLA-A and HLA-B loci.