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 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.
Gobin
S J
SJ
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
Keijsers
V
V
van Zutphen
M
M
van den Elsen
P J
PJ
D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D004742:Enhancer Elements, Genetic / Q000276:immunology* / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology; D005805:Genes, MHC Class I / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D015533:Transcriptional Activation / Q000276:immunology*; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel