Genetic Studies on Mammalian DNA Methyltransferases
Genetic Studies on Mammalian DNA Methyltransferases
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DOI：
10.1007/978-3-319-43624-1_6
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Chen, Taiping
中科院分区：
文献类型：
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作者：
Dan, Jiameng;Chen, Taiping
C5 位胞嘧啶甲基化产生 5-甲基胞嘧啶 (5mC)，是在许多真核生物中发现的 DNA 修饰，包括真菌、植物、无脊椎动物和脊椎动物，尽管其水平在不同生物中差异很大。在哺乳动物中，胞嘧啶甲基化主要发生在 CpG 二核苷酸中，其基因组中的大多数 (60-80%) CpG 位点都被甲基化。 DNA 甲基化在染色质结构和基因表达的调节中起着至关重要的作用，对于哺乳动物的发育至关重要。 DNA 甲基化水平和模式的异常变化与多种人类疾病有关，包括癌症和发育障碍。在哺乳动物中，DNA 甲基化由三种活性 DNA 甲基转移酶 (Dnmts) 介导，即 Dnmt1、Dnmt3a 和 Dnmt3b。在过去的二十年里，对小鼠体内这些酶及其调节因子的基因操作极大地促进了我们对哺乳动物 DNA 甲基化生物学功能的理解。在本章中，我们讨论哺乳动物 Dnmt 的遗传学研究，重点关注它们在胚胎发生、细胞分化、基因组印记和 X 染色体失活中的作用。
Cytosine methylation at the C5-position, generating 5-methylcytosine (5mC), is a DNA modification found in many eukaryotic organisms, including fungi, plants, invertebrates, and vertebrates, albeit its levels vary greatly in different organisms. In mammals, cytosine methylation occurs predominantly in the context of CpG dinucleotides, with the majority (60-80 %) of CpG sites in their genomes being methylated. DNA methylation plays crucial roles in the regulation of chromatin structure and gene expression and is essential for mammalian development. Aberrant changes in DNA methylation levels and patterns are associated with various human diseases, including cancer and developmental disorders. DNA methylation is mediated by three active DNA methyltransferases (Dnmts), namely, Dnmt1, Dnmt3a, and Dnmt3b, in mammals. Over the last two decades, genetic manipulations of these enzymes, as well as their regulators, in mice have greatly contributed to our understanding of the biological functions of DNA methylation in mammals. In this chapter, we discuss genetic studies on mammalian Dnmts, focusing on their roles in embryogenesis, cellular differentiation, genomic imprinting, and X-chromosome inactivation.