CLONING AND SEQUENCING OF A CDNA-ENCODING DNA METHYLTRANSFERASE OF MOUSE CELLS - THE CARBOXYL-TERMINAL DOMAIN OF THE MAMMALIAN ENZYMES IS RELATED TO BACTERIAL RESTRICTION METHYLTRANSFERASES
CLONING AND SEQUENCING OF A CDNA-ENCODING DNA METHYLTRANSFERASE OF MOUSE CELLS - THE CARBOXYL-TERMINAL DOMAIN OF THE MAMMALIAN ENZYMES IS RELATED TO BACTERIAL RESTRICTION METHYLTRANSFERASES
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DOI：
10.1016/0022-2836(88)90122-2
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发表时间：
1988-10-20
影响因子：
5.6
通讯作者：
INGRAM, V
中科院分区：
文献类型：
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作者：
BESTOR, T;LAUDANO, A;INGRAM, V
克隆并测定了小鼠细胞DNA(胞嘧啶-5)甲基转移酶(DNA MeTase)的基因序列。该核苷酸序列含有一个开放阅读框，足以编码一个由1573个氨基酸残基组成的多肽，这与在小鼠细胞中发现的最大DNA MeTase物种的表观大小接近。推测的蛋白质序列的羧基末端570个氨基酸残基与细菌II型DNA胞嘧啶甲基转移酶有惊人的相似之处，似乎代表了一个催化甲基转移酶结构域。该分子的氨基末端部分可能参与调节羧基末端甲基转移酶结构域的活性，因为针对该区域内的肽序列的抗体在体外抑制转甲基酶的活性。在所测试的所有小鼠细胞类型中都发现了5200碱基DNA MeTase特异性mRNA的表达，并且已知具有不同基因组甲基化模式的细胞系含有相似或相同大小和从头序列特异性的DNA MeTase蛋白。讨论了这些发现对于理解建立和维持甲基化模式所涉及的机制的影响。
A cDNA encoding DNA (cytosine-5)-methyltransferase (DNA MeTase) of mouse cells has been cloned and sequenced. The nucleotide sequence contains an open reading frame sufficient to encode a polypeptide of 1573 amino acid residues, which is close to the apparent size of the largest species of DNA MeTase found in mouse cells. The carboxyl-terminal 570 amino acid residues of the inferred protein sequence shows striking similarities to bacterial type II DNA cytosine methyltransferases and appears to represent a catalytic methyltransferase domain. The amino-terminal portion of the molecule may be involved in regulating the activity of the carboxy-terminal methyltransferase domain, since antibodies directed against a peptide sequence located within this region inhibits transmethylase activity in vitro. A 5200 base DNA MeTase-specific mRNA was found to be expressed in all mouse cell types tested, and cell lines known to have different genomic methylation patterns were found to contain DNA MeTase proteins of similar or identical sizes and de novo sequence specificities. The implications of these findings for an understanding of the mechanisms involved in the establishment and maintenance of methylation patterns are discussed.