中文摘要
DNA甲基化作为重要表观遗传机制调控基因的表达,其以多种修饰方式(5mC,6mA和4mC等)广泛存在于多种生物中,影响一系列的生物学过程。在之前研究中我们首次证明果蝇基因组DNA中存在6mA修饰,并发现哺乳动物TET蛋白在果蝇中唯一同源物DMAD为6mA去甲基化酶,果蝇的早期胚胎基因组中富含6mA并可能存在6mA的主动去甲基化过程,且DMAD在早期胚胎中具有调控6mA去甲基化的活性且其表达量需精确调控。这一系列证据提示6mA及DMAD可能在早期胚胎发生发育过程中扮演重要角色。在此基础上本研究将以果蝇早期胚胎发育阶段中的6mA修饰为研究内容,绘制果蝇早期胚胎发育过程中的6mA动态图谱,详细分析6mA是如何改变转录抑制或激活状态来推动早期胚胎发育由母型向合子型转变,揭示6mA在果蝇早期胚胎发育中所发挥的具体功能及调控机制,同时也将进一步加深我们对6mA在高等真核生物中调控功能的理解。
英文摘要
DNA methylation, an epigenetic mechanism, regulates gene expression and a variety of cellular processes. Several methylated bases, including 5-methylcytosine (5mC), N6-methyladenine (6mA) and N4-methylcytosine (4mC), have been found in genomic DNA from diverse species. In our previous study, we found that 6mA is present in the Drosophila DNA. Moreover, we showed that the dynamic change of 6mA modification during embryonic development may involve an active demethylation event. The DMAD expression must be under tight control during embryonic development. Thus, our previous findings suggest that 6mA modification mediated by DMAD possibly contributes to early embryonic development. In this study, we focus on the 6mA methylome of Drosophila early embryos at multiple early embryonic stages. We characterize the epigenetic landscapes of 6mA modification in early Drosophila embryos, and answer an intriguing issue of whether and how 6mA modification contributes to gene expression in Maternal-zygotic Transition. We will uncover biological function and regulatory mechanism of 6mA DNA modification mediated by DMAD in Drosophila early embryogenesis. This research will also evidently expand our knowledge of potential role of 6mA in higher eukaryotes.
