Sjp. Gobin et al., THE ROLE OF ENHANCER-A IN THE LOCUS-SPECIFIC TRANSACTIVATION OF CLASSICAL AND NONCLASSICAL HLA CLASS-I GENES BY NUCLEAR FACTOR KAPPA-B, The Journal of immunology (1950), 161(5), 1998, pp. 2276-2283
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.