The Role of Enhancer A in the Locus-Specific Transactivation of Classical and Nonclassical HLA Class I Genes by Nuclear Factor κB

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 κB motifs of enhancer A (κB1 and κB2) 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-κB-induced route of transactivation. It was shown that NF-κB-induced transactivation through enhancer A is most important for the HLA-A locus, which contains two NF-κB binding sites. Although the enhancer A of HLA-B contains only one NF-κB binding site (κB1), there was still a moderate transactivation by NF-κB. Since HLA-F, which also possesses one NF-κB binding site but lacks protein binding to its κB2 site, was not transactivated by NF-κB, the NF-κB-mediated transactivation through the κB1 motif in HLA-B is most probably facilitated by binding of the transcription factor Sp1 to the upstream κB2 site. Thus, transcriptional regulation of HLA class I genes by NF-κB is restricted to the HLA-A and HLA-B loci.