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The human leukocyte antigen A2 interferon-stimulated response element consensus sequence binds a nuclear factor required for constitutive expression.

J F Waring·J E Radford·L J Burns·G D Ginder
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Abstract

Both constitutive and interferon-inducible enhancer-like elements have been identified previously in the promoter of human leukocyte antigen (HLA) class I genes. One of these sites is termed the interferon-stimulated response element (ISRE). We have tested the function of an ISRE consensus sequence in the human HLA class I gene HLA-A2 and confirmed previous studies that showed that the HLA-A2 ISRE consensus sequence does not mediate a response to interferons. However, deletion of the ISRE consensus sequence caused a several-fold reduction in the constitutive expression of the HLA-A2 gene in K562 and Jurkat cells. Mobility shift assays performed with the HLA-A2 ISRE revealed the presence of a constitutive binding protein (ISRE/CBP). This protein binds specifically to the HLA-A2 ISRE sequence, and binding is not efficiently competed by the ISRE sequences of the HLA-B7 or ISG54 genes. Substitution of the HLA-B7 or ISG54 ISRE sequences for the HLA-A2 ISRE sequence caused a severalfold reduction in the constitutive expression of the HLA-A2 gene. Mass determinations showed the ISRE/CBP to be 105 kDa, different than any previously characterized ISRE binding proteins. We propose that ISRE/CBP is a novel positive transcriptional regulatory factor for the HLA-A2 gene that may contribute to the differential expression of HLA-A versus HLA-B genes.

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Base SequenceBinding SitesCarrier ProteinsConsensus SequenceEnhancer Elements, GeneticGene Expression RegulationGene Expression Regulation, NeoplasticGenes, MHC Class IHLA-A2 AntigenHLA-B7 AntigenHumansInterferon-gammaLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia-Lymphoma, Adult T-CellMolecular Sequence DataMolecular WeightMutagenesis, Site-DirectedNeoplasm ProteinsProtein BindingSequence AlignmentTumor Cells, CulturedComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J F Waring, J E Radford, L J Burns, G D Ginder. 1995-05-19. The human leukocyte antigen A2 interferon-stimulated response element consensus sequence binds a nuclear factor required for constitutive expression.. https://doi.org/10.1074/jbc.270.20.12276

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