组蛋白H3K4甲基转移酶Mll2/Wbp7参与造血免疫组织发育分化的功能与机制研究

项目名称： 组蛋白H3K4甲基转移酶Mll2/Wbp7参与造血免疫组织发育分化的功能与机制研究

项目编号： No.31471207

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 张岩

作者单位： 中国科学院上海巴斯德研究所

项目金额： 90万元

中文摘要： 组蛋白翻译后修饰调控着基因的表达，参与了多种组织与器官的发育分化。组蛋白H3K4位点的三甲基化是基因转录激活的重要标志，在进化中保守的Trithorax蛋白质家族是该位点特异性的甲基转移酶。在哺乳动物中，Trithorax蛋白家族共有7个成员：MLL,MLL2,MLL3,Mll4,Mll5,Set1a与Set1b。过去的研究发现，Trithorax蛋白家族成员参与调控了造血免疫组织的分化与发育：其中，Mll与Mll5参与了造血干细胞的自我更新；此外，Mll参与了2型记忆性助T淋巴细胞的激活，Mll5参与调控了自然杀伤与自然杀伤T淋巴细胞的发育，Mll2参与了巨噬细胞的活性调节。在本项目中，我们将研究Mll2在造血干细胞的功能维持与CD4+T细胞的发育分化过程中的功能与分子机制。这项研究，不仅将进一步阐明造血免疫组织发育分化的表观遗传调控机制，也将为相关疾病诊治提供重要的理论基础与实验依据。

中文关键词： 组蛋白修饰；组蛋白甲基化；表观遗传调控

英文摘要： Histone post-trnaslational modifications regulates gene transcription or silencing during the development and differentiation of multiple tissues and organs. Histone H3K4 tri-methylation is a hallmark of gene transcriptional activation, and evolutionary conserved Trithorax group proteins are the histone methyltransferases catalyzes H3K4. In mammals, there have at least seven trithorax group proteins have been identified: Mll, Mll2, Mll3, Mll4, Mll5,Set1a and Set1b. Several previous studies have found that Trithorax group proteins regulate the development and differentiation of hematopoietic and immune cells:both Mll and Mll5 control the self-renewal of hematopoietic stem cells. Moreover, Mll is required for the maintenance of memory T helper type 2 cell responses, and Mll5 is required for the development of natural killer and natural killer T lymphocytes.More recently, Mll4 has been found to control the macrophage activation.In this project, we will investigate the functional role of Mll2 particularly in the development and differentiation of hematopoietic stem cell and naive CD4+ T helper cells. This study will provide important insights not only into the developmental role of histone modifying enzymes but also into their clinical significance/relevance in human developmental diseases.

英文关键词： Histone Modification;Histone Methylation;Epigenetic Regulation