Tet双加氧酶在哺乳动物表观遗传调控中的作用

Roles of Tet proteins in mammalian epigenetic regulation

DNA甲基化作为一种重要的表观遗传修饰,在哺乳动物的生长发育过程中发挥着举足轻重的功能。DNA甲基化谱式并不是一成不变的,个体发育过程中甲基化谱式如何建立以及如何逆转从而实现基因时空特异性表达,一直是表观遗传领域的重大科学问题。课题以"干细胞全能性建立的表观遗传调控研究"为主要脉络,阐明了Tet双加氧酶介导的DNA去甲基化过程及其在细胞命运决定和哺乳动物发育中的功能。现将对项目启动五年来该课题的主要原创性工作进行综述。

DNA methylation, as an important epigenetic mark, plays crucial roles during development in mammals. Though 5-methylcytosine （SmC） is relatively stable, genome-wide DNA methylation reprogramming has been observed in two developmental stages during embryogenesis. The mechanism of the establishment and reversal of genomic DNA methylation patterns has remained a major scientific question in the field of epigenetics. Our group has focused on the epigenetic mechanism of establishment of pluripotent stem cell identity and has elucidated the Tet dioxygenase mediated DNA demethylation pathway as well as its role in cell fate transition and development in mammals. This article attempts to review the research progress of the five-year project.