The role of mammalian DNA methyltransferases in the regulation of gene expression.
The role of mammalian DNA methyltransferases in the regulation of gene expression.
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DOI：
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发表时间：
2005
影响因子：
8.3
通讯作者：
J. Turek-Plewa;P. Jagodziński
中科院分区：
文献类型：
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作者：
J. Turek-Plewa;P. Jagodziński
术语表观遗传修饰表示不包括DNA序列改变的基因表达的可逆性状。这些表观遗传学改变负责染色质结构稳定性、基因组完整性、组织特异性基因表达的调节、胚胎发育、基因组印记和女性X染色体失活。表观遗传变化包括可逆的DNA甲基化和组蛋白乙酰化或甲基化。哺乳动物基因组DNA的修饰包括胞嘧啶-鸟嘌呤二核苷酸（CpG）内胞嘧啶（C）残基5位的甲基化，导致形成5-甲基胞嘧啶（m5 C）。脊椎动物中的调节DNA序列通常很少或没有甲基化。DNA甲基转移酶（DNMTs）催化哺乳动物基因组DNA甲基化，在启动染色质重塑和基因表达调控中发挥特殊作用。哺乳动物的DNMT是DNMT 1、DNMT 3A和DNMT 3B，它们与辅助蛋白如DNMT 3L一起负责配子发生、胚胎发生和体细胞组织发育期间的甲基化模式获取。可逆的表观遗传学改变通过在配子发生、胚胎发生和细胞分化期间激活或失活功能基因的转录而导致基因组信息的选择性利用。最近，在人类体细胞以及女性和男性生殖细胞中鉴定了DNMT 1的几种不同的亚型。DNMT在表观遗传DNA变化中的功能研究的最新进展已经形成了理解各种疾病病因的基础，因此，已经促进并实现了关于这些疾病的新疗法。
The term epigenetic modification denotes reversible traits of gene expression that do not include alterations to the DNA sequence. These epigenetic alterations are responsible for chromatin structure stability, genome integrity, modulation of tissue-specific gene expression, embryonic development, genomic imprinting and X-chromosome inactivation in females. Epigenetic changes include reversible DNA methylation and histone acetylation or methylation. The modification of mammalian genomic DNA includes the methylation at the 5-position of the cytosine (C) residue within cytosine-guanine dinucleotides (CpG), resulting in the formation of 5-methylcytosine (m5C). Regulatory DNA sequences in vertebrates often have little or no methylation. The methylation of mammalian genomic DNA is catalyzed by DNA methyltransferases (DNMTs), which play a special role in the initiation of chromatin remodeling and gene expression regulation. The mammalian DNMTs are DNMT1, DNMT3A and DNMT3B, which together with accessory proteins, like DNMT3L, are responsible for methylation pattern acquisition during gametogenesis, embryogenesis and somatic tissue development. Reversible epigenetic alterations lead to selective utilization of genome information through the activation or inactivation of transcription of functional genes during gametogenesis, embryogenesis and cell differentiation. Recently, several disparate isoforms of DNMT1 were identified in human somatic and female and male germ cells. Recent advances in the investigation of DNMT function in epigenetic DNA changes have formed the basis of the understanding of various disorder etiopathogeneses, and as a result, have facilitated and enabled new therapies with respect to these diseases.