哺乳动物DNA甲基化及其在体细胞诱导重编程中的作用

Mammalian DNA methylation and its roles during the induced reprogramming of somatic cells

诱导多能干细胞(Induced pluripotent stem cell,iPS)技术提供了将终末分化的细胞逆转为多潜能干细胞的可能,在干细胞基础理论研究和再生医学中具有重要意义。然而,目前体细胞诱导重编程方法效率极低,常发生不完全的重编程。研究表明,在不完全重编程的细胞中存在体细胞的表观遗传记忆,而DNA甲基化作为相对长期和稳定的表观遗传修饰,是影响重编程效率和iPS细胞分化能力的重要因素之一。哺乳动物DNA甲基化是指胞嘧啶第五位碳原子上的甲基化修饰,常发生于CpG位点。DNA甲基化能够调节体细胞特异基因和多能性基因的表达,因此其在哺乳动物基因调控、胚胎发育和细胞重编程过程中发挥着重要作用。此外,异常DNA甲基化可能导致iPS细胞基因印记的异常和X染色体的失活。文章重点围绕DNA甲基化的机制、分布特点、及其在体细胞诱导重编程中的作用进行了综述。

The technology of induced pluripotent stem cell （iPS） provides the possibility to reverse the terminal differenti-ated cells to pluripotent stem cells, and is therefore of great importance in both the theoretical research of stem cells and regenerative medicine. However, the efficiency of current induced reprogramming methods is extremely low, and the in-complete reprogramming often happens. It has been reported that some epigenetic memory of the somatic cells exists in these incomplete reprogrammed iPS cells, and DNA methylation, as a relative long-term and stable epigenetic modification, is one of the important factors that influence the efficiency of reprogramming and differentiative capacity of iPS cells. Mammalian DNA methylation, which normally appears on the CpG sites, occurs on the fifth carbon atom of the cytosine ring. DNA methylation can modulate the expression of somatic cell specific genes, and pluripotent genes;hence, it plays＆amp;nbsp;important roles in the processes of mammalian gene regulation, embryonic development and cell reprogramming. In addi-tion, it has also been found that abnormal DNA methylation may lead to the disorder of genetic imprinting and the inactiva-tion of X chromosome in iPS cells. Therefore, in order to provide a concise guidance of DNA methylation studies in iPS, we mainly review the mechanism, the distribution features of DNA methylation, and its roles in induced reprogramming of somatic cells.