Role of cytidine deaminases in epigenetic reprogramming and demethylation of DNA

人类和其他哺乳动物基因组中的所有基因现在都是已知的。然而，在一个新的有机体从胚胎到成人的发育过程中，我们对哪些信号是基因开启和关闭所需要的知之甚少。一个重要的信号是以小化学分子（甲基）的形式附着在DNA上的指令。当需要关闭时，它们通常会附着在基因上。当基因需要开启时，甲基需要从DNA中移除；这在胚胎发育初期尤其重要。当这种转换有缺陷时，它会引起胚胎发育疾病，许多癌症具有异常的表观遗传？该类型的切换。我们目前的工作已经确定了一种从DNA中去除甲基信号的机制，在这项资助下的工作中，我们将更好地了解这种机制在胚胎中的作用，以便利用其活动进行干细胞再生。治疗癌症的药物和方法。

All genes in the genome of humans and other mammals are now known. However we have little knowledge about which signals are needed for genes to switch on and off during development of a new organism from embryo to adult. An important signal are instructions that are attached to DNA in the form of small chemical molecules (methyl-groups). These are usually attached to genes when they need to be off. When genes need to be switched on, the methyl-groups need to be removed from the DNA; this is particularly important at the beginning of development in the very early embryo. When this switching is defective it can give rise to diseases of embryonic development and many cancers have aberrant ?epigenetic? switching of this type. Our current work has identified a mechanism for the removal of the methyl-signals from DNA, and in work under this grant we will gain a better understanding how this mechanism works in embryos, in order to harness its activities for stem cell ?regenerative? medicine and cures for cancer.