RREB-1 is a transcriptional repressor of HLA-G.
The nonclassical HLA-G is a molecule specifically involved in immune tolerance with highly restricted tissue distribution in healthy conditions. Yet it is overexpressed in numerous tumors and in allografts with better acceptance. Major mechanisms involved in regulation of HLA-G transcription are still poorly described. Thus, to characterize these mechanisms we have developed a specific proteomic approach to identify proteins that bind differentially to the HLA-G gene promoter by promoter pull-down assay followed by spectrometry mass analysis. Among specific binding factors, we focused on RREB-1, a ras-responsive element binding protein 1. We demonstrated that RREB-1 represses HLA-G transcriptional activity and binds three ras response elements within the HLA-G promoter. RREB-1 protein, specifically in HLA-G-negative cells, interacts with subunits of CtBP complex implicated in chromatin remodeling. This demonstration is the first of a repressor factor of HLA-G transcriptional activity taking part in HLA-G repression by epigenetic mechanisms.
Flajollet
Sébastien
S
Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, IBM, Service de Recherches en Hémato-Immunologie, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 75010 Paris, France.
Poras
Isabelle
I
Carosella
Edgardo D
ED
Moreau
Philippe
P
D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D024202:Electrophoretic Mobility Shift Assay; D044127:Epigenesis, Genetic; D015870:Gene Expression; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C101743:RREB1 protein, human; D014157:Transcription Factors