DNA甲基化调控的转录因子EGR1对树突状细胞的功能调控研究

项目名称： DNA甲基化调控的转录因子EGR1对树突状细胞的功能调控研究

项目编号： No.31200654

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 免疫学

项目作者： 张迁

作者单位： 中国医学科学院基础医学研究所

项目金额： 25万元

中文摘要： 树突状细胞（DC）为专职抗原提呈细胞，抗原吞噬与加工能力强，但抗原提呈能力弱，当其被感染信号活化后，成熟DC高分泌细胞因子，抗原提呈能力显著增强，可以有效激活T细胞，因此DC是连接天然免疫和适应性免疫的桥梁。基于本课题组建立的人DC分化成熟的全基因组甲基化组和转录组的数据平台，本课题旨在研究DC成熟信号如何完成从胞外经胞浆传递入核，在染色质水平介导表观遗传改变，来调控关键基因的转录，建立起DC特异性的功能状态。通过对DC甲基化谱的分析，发现DC成熟过程中，转录因子EGR1的启动子区存在DNA甲基化变化的区域，针对这一现象，拟研究感染信号如何诱导EGR1启动子区DNA甲基化的改变，DNA甲基化是否参与调控EGR1的转录，EGR1作为转录因子又如何参与调控DC的成熟，从而揭示感染信号如何诱导表观遗传改变来建立成熟DC特有的基因表达模式，从而解释未成熟DC与成熟DC的功能状态转变的机制。

中文关键词： DNA甲基化；组蛋白修饰；转录因子；天然免疫；树突状细胞

英文摘要： Dendritic cells (DCs) are the most important professional antigen-presenting cells. immature DCs(imDCs) are characterized by high endocytic activity and low T-cell activation potential.when activated by pathogens through pattern recognition receptors (PRRs) such as Toll-like receptor 4 (TLR4) signaling, imDC will become maturation(mDCs) characterized by highly expressing kinds of cytokines and co-stimulatory factors and high ability to present antigens to and activate T cells.How do maturation signal induce this functional switch between immature DC and mature DC? To answer this question from the point of view of epigenetic regulation,we have established DNA methylome and transcriptome of imDCs and mDCs. Take advantage of the database, we have found that a region in the promoter of egr1 undergone upregulated DNA methylation level during DC maturation. This study will reveal that how infection signal induce change of DNA methylation level in the promoter of egr1, and whether high methylated promoter of egr1 repress transcription of egr1. we will also find the targets of EGR1 in DCs and reveal how EGR1 repress the maturation of DC. From this study we will start to know that how infection of pathgen pass signal from plasm membrane to nucleus, and establish special epigenetic regulation network in the level of chrom

英文关键词： DNA methylation；histone modification；transcription factor；innate immunity；dendritic cell