1型糖尿病患者CD4+T细胞组蛋白3乙酰化变化及机制研究

项目名称： 1型糖尿病患者CD4+T细胞组蛋白3乙酰化变化及机制研究

项目编号： No.81200580

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 侯粲

作者单位： 中南大学

项目金额： 23万元

中文摘要： 本课题所在实验室已证实1型糖尿病的发生发展受到DNA甲基化及组蛋白修饰的影响，然而其机制尚未完全阐明。我们发现成人隐匿性自身免疫糖尿病患者CD4+T细胞组蛋白3（H3）整体乙酰化水平降低，组蛋白乙酰转移酶及组蛋白去乙酰化酶（HDAC）HDAC5等表达异常，Foxp3基因启动子区H3乙酰化水平下调。本研究拟在前期试验的基础上，检测1型糖尿病患者CD4+T细胞整体H3乙酰化水平及组蛋白修饰酶谱，利用ChIP-on-chip技术建立1型糖尿病患者CD4+T细胞基因H3乙酰化图谱；分析HDAC5对1型糖尿病患者CD4+T细胞Foxp3基因调控机制；探讨1型糖尿病患者CD4+T 细胞H3乙酰化敏感基因与组蛋白乙酰转移酶及去组蛋白去乙酰化酶的相互作用和调控模式；筛查鉴定与1型糖尿病相关的H3乙酰化关键分子及其调控网络。本项目将有助于进一步阐明CD4+T细胞H3乙酰化与1型糖尿病发病的分子机制。

中文关键词： 自身免疫糖尿病；T细胞；基因组；组蛋白乙酰化；FOXP3

英文摘要： Our laboratory has confirmed that the DNA methylation and histone modification was abnormal in Type 1 diabetes. However, its mechanism has not yet been fully elucidated. Our previous studies found Histone 3 (H3) acetylation was reduced in CD4+ T cell from latent autoimmune diabetic patients. The level of histone deacetylase(HDAC) HDAC2, HDAC5, and SIRT1 mRNA was upregulated, the level of histone acetyltransferase P300, CREBBP and PCAF mRNA was downregulated，the level of H3 acetylation at the promoter region of Foxp3 gene was decreased .Based on the previous research results,we will detect the global H3 acetylation levels and the histone acetyltransferase enzymes and the histone deacetylase enzymes in CD4+ T cells from type 1 diabetic patients.We will use the ChIP-on-chip technology to establish H3 acetylation gene maps. The purpose of the study is to find the histone acetylaiton pattern in CD4+ T cells from type 1 diabetic patients, to explore the interactions and regulation mode among H3 acetylation-sensitive genes,histone acetyltransferase and histone deacetylase enzymes.We aim at screening and identifying the key molecules of H3 acetylation and regulatory networks. The project will be helpful to explain the molecular mechanisms of type 1 diabetes and H3 acetylation. In addition, it may contribute to discover

英文关键词： autoimmune diabetes；T cells；genome；histone acetylation；FOXP3