组蛋白甲基化酶复合物COMPASS催化的H3K4me2,H3K4me3对果蝇发育调控的研究

项目名称： 组蛋白甲基化酶复合物COMPASS催化的H3K4me2,H3K4me3对果蝇发育调控的研究

项目编号： No.31200964

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 肖裕

作者单位： 中国科学院昆明动物研究所

项目金额： 21万元

中文摘要： 组蛋白H3第四位赖氨酸的三甲基化(H3K4me3)是重要的表观遗传学标记，它作为转录活性的标记普遍存在于基因启动子区，但亦有例外，而二甲基化(H3K4me2)的研究较少。 绝大多数的H3K4甲基化是由COMPASS复合物催化的，它包括四个核心组分：SET1/MLL，RbBP5, ASH2 和WDR5。在线虫的研究表明H3K4me2,H3K4me3有重要的发育生物学功能。本研究将运用多种方法研究野生型果蝇和COMPASS核心组分分别敲除的突变体。主要通过定量免疫荧光技术对胚胎中的体细胞和生殖细胞的H3K4甲基化水平进行对比，还将研究H3K4甲基化缺失对果蝇寿命，基因组稳定性，生殖能力的影响。通过本研究能揭示H3K4甲基化对果蝇的发育的影响，并比较H3K4me2和H3K4me3的不同调控模式。

中文关键词： 表观遗传学；组蛋白修饰；甲基化；DNA调控元件；染色质沉默

英文摘要： Trimethyls on histone 3 lysine 4(H3K4) are important epigenetic marks associated with gene activation and located in the promoter region in ative genes but with few exceptions. However the fuction of dimethyls on H3K4 is still elusive. In most of cases the methylation on H3K4 is catalysed by SET1(Su(var), Enhancer of zeste and Trithorax1) and/or MLL(Mixed Lineage Leukemia) or their homologs. In cells SET1/MLL and other factors form a large protein complex named COMPASS (Complex Proteins Associated with Set1/MLL). SET1/MLL, RbBP5, Ash2L, and WDR5 are core components within the COMPASS. The COMPASS was originally purified and identified in yeast. The COMPASS was characterized mostly in yeast and cultured mammalian cells and therefore its function in developmental context was poorly understood. However recent studies in C.elegans have demonstrated that the COMPASS, i.e. H3K4me2 and H3K4me3, plays important and multiple roles in longevity, genome stability, reproduction capacity et al. In this project we will study the function of COMPASS in the early stages during Drosophila melanogaster development to understand respective role of each of the core components in the COMPASS. Quantatvie immunofluorescnce will be applied to compare the H3K4me2 and H3K4me3 localizaiton （soma and germ cells） and levels in wildtype and

英文关键词： epigenetics；histone modification；methylation；DNA regulatory element；chromatin silencing