Differential transcription inducibility by interferon of the HLA-A3 and HLA-B7 class-I genes.
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.
Hakem
R
R
Centre d'Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, France.
Jezo-Brémond
A
A
Le Bouteiller
P
P
Harper
K
K
Lemonnier
F A
FA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D015791:HLA-A3 Antigen / Q000235:genetics*; D015793:HLA-B7 Antigen / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000235:genetics; D015183:Restriction Mapping; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D015791:HLA-A3 Antigen; D015793:HLA-B7 Antigen; D007370:Interferon Type I; D015345:Oligonucleotide Probes; D012334:RNA, Neoplasm; D015500:Chloramphenicol O-Acetyltransferase