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In vivo, RFX5 binds differently to the human leucocyte antigen-E, -F, and -G gene promoters and participates in HLA class I protein expression in a cell type-dependent manner

Dausset, Jean
Carosella, E. D.
Moreau, Philippe
Published in Immunology. 2004, vol. 111, no. 1, p. 53-65
Abstract We analysed the regulation of human leucocyte antigen (HLA)-E, -F and -G genes, focusing on the SXY module, a promoter region that controls major histocompatibility complex (MHC) class II expression and participates in the expression of classical HLA class I molecules. It comprises the X1, X2 and Y boxes, bound by RFX, X2-BP/ATF/CREB and NFY factors, respectively. The complex recruits the master control factor CIITA. The SXY module is conserved in HLA-E and HLA-F gene promoters, whereas in the HLA-G promoter, the only conserved boxes are S and X1. Chromatin immunoprecipitation assays, performed on HLA-G positive and negative cell lines, demonstrated the in situ binding of RFX5 and CIITA to HLA-E and HLA-F, but not to HLA-G, promoters. In B cells from bare lymphocyte syndrome patients lacking RFX5 or CIITA, we observed lower steady-state levels of HLA-E and HLA-F transcripts but did not find any significant decrease in the cell-surface expression of HLA-E/classical HLA class I. In RFX5-deficient fibroblasts, the cell-surface expression of HLA molecules was decreased. RFX5 and CIITA are thus not involved in HLA-G expression and their importance for the surface expression of HLA-E/classical HLA class I molecules may vary depending on the cell type.
Keywords B-Lymphocytes/ metabolismCell Line, TransformedCell Line, TumorDNA-Binding Proteins/ metabolismFibroblasts/metabolismFlow CytometryGenes, MHC Class IHLA Antigens/geneticsHistocompatibility Antigens Class I/geneticsHumansImmunoblotting/methodsNuclear ProteinsPrecipitin Tests/methodsPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionTrans-Activators/ metabolism
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PMID: 14678199
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