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

• Published in: The Journal of immunology (1950) 1998-09, Vol.161 (5), p.2276-2283
• Main Authors: Gobin, S J, Keijsers, V, van Zutphen, M, van den Elsen, P J
• Format: Article
• Language: English
• Subjects: Binding Sites - genetics; Binding Sites - immunology; Enhancer Elements, Genetic - immunology; Enhancer Elements, Genetic - physiology; Gene Expression Regulation - immunology; Genes, MHC Class I - immunology; HLA Antigens - genetics; HLA Antigens - metabolism; HLA-A Antigens - genetics; HLA-B Antigens - genetics; Humans; NF-kappa B - metabolism; NF-kappa B - physiology; Protein Binding - genetics; Protein Binding - immunology; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-rel; Transcriptional Activation - immunology; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.5.2276

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.