Two major forms of DNA (cytosine-5) methyltransferase in human somatic tissues
Two major forms of DNA (cytosine-5) methyltransferase in human somatic tissues
复制标题
DOI：
10.1073/pnas.96.17.9751
复制
发表时间：
1999-08-17
影响因子：
11.1
通讯作者：
Shen, CKJ
中科院分区：
文献类型：
--
作者：
Hsu, DW;Lin, MJ;Shen, CKJ
到目前为止，只有一种主要形式的脊椎动物DNA(胞嘧啶-5)甲基转移酶(CpG MTase，EC 2.1.1.37)被鉴定、克隆和广泛研究。这种名为DNMT1的酶被认为负责脊椎动物体细胞中的大部分维持以及从头开始的甲基化活动。我们现在报告在不同类型的人类细胞系和体细胞组织中发现了另一种丰富的CpG MTase。有趣的是，编码这个CpG MTase的mRNA是由Dnmt1基因的初级转录产物选择性剪接而来的，Dnmt1基因在外显子4和5之间额外包含48个核苷酸，此外，这个48个核苷酸的外显子序列来自于位于内含子4的一组不同Alu重复序列的第一个或最上游拷贝。通过半定量逆转录-PCR分析估计，该mRNA的表达与先前已知的较短的Dnmt1基因的表达的比率在三分之二到七分之三之间。Dnmt1转录本的这种选择性剪接方案似乎在高等灵长类动物中是保守的。我们建议将最初描述的和最近发现的CpG MTase分别命名为DNMT1-a和DNMT1-b。这一发现的进化和生物学意义与CpG残基和CpG MTase的细胞功能有关。
Thus far, only one major form of vertebrate DNA (cytosine-5) methyltransferase (CpG MTase, EC 2.1.1.37) has been identified, cloned, and extensively studied. This enzyme, dnmt1, has been hypothesized to be responsible for most of the maintenance as well as the de novo methylation activities occur ring in the somatic cells of vertebrates. We now report the discovery of another abundant species of CpG MTase in various types of human cell lines and somatic tissues. Interestingly, the mRNA encoding this CpG MTase results from alternative splicing of the primary transcript from the Dnmt1 gene, which incorporates in frame an additional 48 nt between exons 4 and 5, Furthermore, this 48-nt exon sequence is derived from the first, or the most upstream, copy of a set of seven different Alu repeats located in intron 4. The ratios of expression of this mRNA to the expression of the previously known, shorter Dnmt1 mRNA species, as estimated by semiquantitative reverse transcription-PCR analysis, range from two-thirds to three-sevenths. This alternative splicing scheme of the Dnmt1 transcript seems to be conserved in the higher primates. We suggest that the originally described and the recently discovered forms of CpG MTase be named dnmt1-a and dnmt1-b, respectively. The evolutionary and biological implications of this finding are discussed in relation to the cellular functions of the CpG residues and the CpG MTases.