Controlled nuclear uptake of DNA methyltransferase and targeting to functional domains within the nucleus

DNA甲基化在基因表达和染色质结构的调节中起着重要作用，是哺乳动物正常发育所必需的。我们已经阐明了DNA甲基转移酶基因(Dnmt1)的结构，并鉴定了各种Dnmt1亚型。在我们确定了将该酶定位于复制点的序列之后，我们已经确定并鉴定了另一个负责该酶在早期发育过程中细胞质保持的区域。我们希望筛选参与发育控制的Dnmt1核摄取及其与核复制中心的关联的相互作用因素。我们已经在ES细胞中引入了各种Dnmt1突变来研究这种调节的机制。通过这种方法，我们还想要研究Dnmt1的受控亚细胞定位在早期发育过程中DNA甲基化模式的变化以及在体细胞中精确复制表观遗传信息中的作用。

DNA methylation plays an important role in the regulation of gene expression and chromatin structure and is essential for normal mammalian development. We have elucidated the structure of the DNA methyltransferase gene (Dnmt1) and have identified various Dnmt1 isoforms. Following on our identification of a sequence targeting the enzyme to replication foci, we have identified and characterized another region that is responsible for cytoplasmic retention of the enzyme during early development. We want to screen for interacting factors that are involved in the developmentally controlled nuclear uptake of Dnmt1 and its association with nuclear replication foci. We have already introduced various Dnmt1 mutations in ES cells to study the mechanisms of this regulation. With this approach we also want to investigate the role of the controlled subcellular localization of Dnmt1 in the change of DNA methaylation patterns during early development and in the precise replication of epigenetic information in somatic cells.