Pradhan Sriharsa, Esteve Pierre-Olivier
New England Biolabs, 32 Tozer Road, Beverly, MA 01915, USA.
Clin Immunol. 2003 Oct;109(1):6-16. doi: 10.1016/s1521-6616(03)00204-3.
Two classes of functional DNA (cytosine-5) methyltransferases have been discovered in mammals to date. One class methylates the unmodified DNA and is designated as the de novo enzyme, whereas the other maintains the methylation status of the daughter strand during DNA replication and thus is referred to as a maintenance DNA methyltransferase. Each enzyme catalyzes methyl group transfer from S-adenosyl-L-methionine to cytosine bases in DNA. During methylation the enzyme flips its target base out of the DNA duplex into a typically concave catalytic pocket. This flipped cytosine base is then a substrate for the enzyme-catalyzed reaction. The newly formed 5-methylcytosine confers epigenetic information on the parental genome without altering nucleotide sequences. This epigenetic information is inherited during DNA replication and cell division. In mammals, DNA methylation participates in gene expression, protection of the genome against selfish DNA, parental imprinting, mammalian X chromosome inactivation, developmental regulation, T cell development, and various diseases.
迄今为止，在哺乳动物中已发现两类功能性DNA（胞嘧啶-5）甲基转移酶。一类使未修饰的DNA发生甲基化，被称为从头合成酶，而另一类在DNA复制过程中维持子链的甲基化状态，因此被称为维持性DNA甲基转移酶。每种酶催化甲基基团从S-腺苷-L-甲硫氨酸转移至DNA中的胞嘧啶碱基上。在甲基化过程中，酶将其靶碱基从DNA双链中翻转出来，进入一个通常呈凹形的催化口袋。然后，这个翻转的胞嘧啶碱基成为酶催化反应的底物。新形成的5-甲基胞嘧啶在不改变核苷酸序列的情况下赋予亲代基因组表观遗传信息。这种表观遗传信息在DNA复制和细胞分裂过程中得以遗传。在哺乳动物中，DNA甲基化参与基因表达、保护基因组免受自私DNA的影响、亲本印记、哺乳动物X染色体失活、发育调控、T细胞发育以及各种疾病。
