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HLA-E is the only class I gene that escapes CpG methylation and is transcriptionally active in the trophoblast-derived human cell line JAR

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Abstract

Polymorphic as well as HLA-F and -G genes are repressed in the human cell line JAR, derived from a tumor of trophoblast origin. By contrast, the HLA-E gene as well as the non-HLA novel coding-sequence, R1, located 5′ to HLA-E, both remain transcriptionally active. We first demonstrated the role of DNA methylation in the repression of class I genes (except HLA-E) in JAR by the use of the 5-Azacytidine demethylating agent. Following treatment, JAR clones reexpressed polymorphic class I transcripts and cell surface α chains. Using methylation-sensitive rare cutter enzymes on JAR genomic DNA, followed by classical or pulse field gel electrophesis and hybridization with HLA locus-specific probes, we found methylated CpG islands in the 5′ region of all class I genes, except for HLA-E. These results, establishing an inverse relationship between states of methylation and transcriptional activity within the MHC class I chromosomal region in JAR, and the observations that the HLA-E and R1 genes were ubiquitously expressed, suggest that the HLA-E chromosomal domain might have functional importance including the presence of housekeeping genes.

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Authors and Affiliations

  1. Laboratoire d'Immunologie, Faculté de Médecine de la Timone, F-13 285, Marseille Cedex 5, France

    José Boucraut (Prof. Dominique Bernard)

  2. Laboratoire d'Hématologie-Immunologie, Hôpital de Pontchaillou, F-35 033, Rennes Cedex, France

    Thierry Guillaudeux & Renée Fauchet

  3. Centre Régional de Transfusion Sanguine, F-35 016, Rennes Cedex, France

    Mehdi Alizadeh & Gilbert Semana

  4. Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, F-13 288, Marseille Cedex 9, France

    Joelle Boretto, Giovanna Chimini & Philippe Le Bouteller

  5. Service d'Ophtalmologie, Hôpital de Rangueil, F-31 000, Toulose Cedex, France

    François Malecaze

  6. CRPG-CNRS, CHU Purpan, F-31 052, Toulouse Cedex, France

    Pierre Pontarotti

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Boucraut, J., Guillaudeux, T., Alizadeh, M. et al. HLA-E is the only class I gene that escapes CpG methylation and is transcriptionally active in the trophoblast-derived human cell line JAR. Immunogenetics 38, 117–130 (1993). https://doi.org/10.1007/BF00190899

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