哺乳动物DNA甲基化及其在体细胞诱导重编程中的作用-遗传.PDFVIP

Hereditas (Beijing) 2014 年 5 月, 36(5): 431―438 综 述 哺乳动物DNA 甲基化及其在体细胞诱导重 编程中的作用 宋红卫, 安铁洙, 朴善花, 王春生 东北林业大学生命科学学院, 哈尔滨 150040 摘要: 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。 关键词: DNA 甲基化; 诱导多能干细胞; 体细胞重编程 Mammalian DNA methylation and its roles during the induced re- programming of somatic cells Hongwei Song, Tiezhu An, Shanhua Piao, Chunsheng Wang College of Life Science, Northeast Forestry University, Harbin 150040, China Abstract: 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, occ