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一级DNA序列决定了哺乳动物DNA甲基转移酶进行维持性甲基化和从头甲基化的位点。

Primary DNA sequence determines sites of maintenance and de novo methylation by mammalian DNA methyltransferases.

作者信息

Bolden A H, Nalin C M, Ward C A, Poonian M S, Weissbach A

出版信息

Mol Cell Biol. 1986 Apr;6(4):1135-40. doi: 10.1128/mcb.6.4.1135-1140.1986.

DOI:10.1128/mcb.6.4.1135-1140.1986
PMID:3023872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC367624/
Abstract

Analysis of the enzymatic methylation of oligodeoxynucleotides containing multiple C-G groups showed that hemimethylated sites in duplex oligomers are not significantly methylated by human or murine DNA methyltransferase unless those sites are capable of being methylated de novo in the single- or double-stranded oligomers. Thus, the primary sequence of the target strand, rather than the methylation pattern of the complementary strand, determines maintenance methylation. This suggests that de novo and maintenance methylation are the same process catalyzed by the same enzyme. In addition, the study revealed that complementary strands of oligodeoxynucleotides are methylated at different rates and in different patterns. Both primary DNA sequence and the spacing between C-G groups seem important since in one case studied, maximal methylation required a specific spacing of 13 to 17 nucleotides between C-G pairs.

摘要

对含有多个C-G基团的寡脱氧核苷酸的酶促甲基化分析表明,双链寡聚物中的半甲基化位点不会被人或鼠DNA甲基转移酶显著甲基化,除非这些位点能够在单链或双链寡聚物中从头甲基化。因此,靶链的一级序列而非互补链的甲基化模式决定了维持甲基化。这表明从头甲基化和维持甲基化是由同一酶催化的相同过程。此外,该研究还揭示,寡脱氧核苷酸的互补链以不同的速率和模式进行甲基化。一级DNA序列和C-G基团之间的间距似乎都很重要,因为在所研究的一个案例中,最大甲基化需要C-G对之间有13至17个核苷酸的特定间距。

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Primary DNA sequence determines sites of maintenance and de novo methylation by mammalian DNA methyltransferases.一级DNA序列决定了哺乳动物DNA甲基转移酶进行维持性甲基化和从头甲基化的位点。
Mol Cell Biol. 1986 Apr;6(4):1135-40. doi: 10.1128/mcb.6.4.1135-1140.1986.
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本文引用的文献

1
Undermethylation at the 5' end of the albumin gene is necessary but not sufficient for albumin production by rat hepatoma cells in culture.白蛋白基因5'端的低甲基化对于培养的大鼠肝癌细胞产生白蛋白是必要的,但并不充分。
Cell. 1982 Oct;30(3):825-33. doi: 10.1016/0092-8674(82)90287-2.
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DNA methylation of three 5' C-C-G-G 3' sites in the promoter and 5' region inactivate the E2a gene of adenovirus type 2.腺病毒2型启动子和5'区域中三个5' C-C-G-G 3'位点的DNA甲基化使E2a基因失活。
Proc Natl Acad Sci U S A. 1984 May;81(10):2950-4. doi: 10.1073/pnas.81.10.2950.
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DNA methylation. Inhibition of de novo and maintenance methylation in vitro by RNA and synthetic polynucleotides.DNA甲基化。RNA和合成多核苷酸在体外对从头甲基化和维持甲基化的抑制作用。
J Biol Chem. 1984 Oct 25;259(20):12437-43.
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Hemimethylated duplex DNAs prepared from 5-azacytidine-treated cells.从经5-氮杂胞苷处理的细胞中制备的半甲基化双链DNA。
Nucleic Acids Res. 1981 Jun 25;9(12):2933-47. doi: 10.1093/nar/9.12.2933.
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DNA methylation: sequences flanking C-G pairs modulate the specificity of the human DNA methylase.DNA甲基化:C-G碱基对侧翼的序列调节人类DNA甲基化酶的特异性。
Nucleic Acids Res. 1985 May 24;13(10):3479-94. doi: 10.1093/nar/13.10.3479.