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RREB-1 Is a Transcriptional Repressor of HLA-G¹

Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, I²BM, Service de Recherches en Hémato-Immunologie, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France

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.

Correspondence: ² Address correspondence and reprint requests to Dr. Philippe Moreau, Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, I²BM Service de Recherches en Hémato-Immunologie, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 75010 Paris, France. E-mail address: philippe.moreau{at}cea.fr

¹ This work was supported by the Commissariat à l'Energie Atomique.