RREB-1 Is a Transcriptional Repressor of HLA-G
RREB-1 Is a Transcriptional Repressor of HLA-G
复制标题
DOI：
10.4049/jimmunol.0902053
复制
发表时间：
2009-12-01
影响因子：
4.4
通讯作者：
Moreau, Philippe
中科院分区：
文献类型：
--
作者：
Flajollet, Sebastien;Poras, Isabelle;Moreau, Philippe
非经典HLA-G是一种特异性参与免疫耐受的分子，在健康条件下具有高度限制的组织分布。然而，它在许多肿瘤和具有更好接受性的同种异体移植物中过表达。参与调节HLA-G转录的主要机制仍然很少描述。因此，为了表征这些机制，我们已经开发了一种特定的蛋白质组学方法，通过启动子下拉测定法，然后通过质谱质谱分析来鉴定与HLA-G基因启动子差异结合的蛋白质。在特异性结合因子中，我们重点关注RREB-1，一种ras反应元件结合蛋白1。我们证明了RREB-I抑制HLA-G转录活性，并结合HLA-G启动子内的三个ras反应元件。RREB-1蛋白，特别是在HLA-G阴性细胞中，与涉及染色质重塑的CtBP复合物亚基相互作用。这是第一个通过表观遗传机制参与HLA-G抑制的HLA-G转录活性抑制因子。免疫学杂志，2009，183：6948-6959.
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-I 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. The Journal of Immunology, 2009, 183: 6948-6959.