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Differential transcription inducibility by interferon of the HLA-A3 and HLA-B7 class-I genes
R Hakem1, A Jezo-Brémond, P Le Bouteiller
1Centre d'Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, France.
HLA-A3 and HLA-B7 class-I genes are differentially regulated in human T lymphoma Jurkat cells, at the transcriptional level, the expression of the HLA-B7 gene being selectively increased following alpha, beta or gamma interferon (IFN) treatment. Using a series of hybrid CAT constructs, associating HLA-A3 and HLA-B7 complete or fragmented promoters, the differential regulation was shown to be associated with 2 nucleotide differences at positions -176 and -175 in the interferon regulatory sequence (IRS) of the HLA-A3 and the HLA-B7 genes. Replacement, using site-directed mutagenesis, of the 2 thymidine in the HLA-A3-IRS by adenine and cytidine found at the same positions in the HLA-B7-IRS was sufficient to restore IFN inducibility of the HLA-A3 promoter and efficient interaction with HeLa nuclear factors. Since the same nucleotide differences are shared by all sequenced HLA-A and HLA-B class-I genes, the differential induction by IFN of the transcription of the HLA-A3 and B7 genes might be a general locus-related property.
HLA-A3 and HLA-B7 class-I genes are differentially regulated in human T lymphoma Jurkat cells, at the transcriptional level, the expression of the HLA-B7 gene being selectively increased following alpha, beta or gamma interferon (IFN) treatment. Using a series of hybrid CAT constructs, associating HLA-A3 and HLA-B7 complete or fragmented promoters, the differential regulation was shown to be associated with 2 nucleotide differences at positions -176 and -175 in the interferon regulatory sequence (IRS) of the HLA-A3 and the HLA-B7 genes. Replacement, using site-directed mutagenesis, of the 2 thymidine in the HLA-A3-IRS by adenine and cytidine found at the same positions in the HLA-B7-IRS was sufficient to restore IFN inducibility of the HLA-A3 promoter and efficient interaction with HeLa nuclear factors. Since the same nucleotide differences are shared by all sequenced HLA-A and HLA-B class-I genes, the differential induction by IFN of the transcription of the HLA-A3 and B7 genes might be a general locus-related property.