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逆转 DNA 甲基化：机制、基因组学和生物学功能。

Reversing DNA methylation: mechanisms, genomics, and biological functions.

机构信息

Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA.

Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA.

出版信息

Cell. 2014 Jan 16;156(1-2):45-68. doi: 10.1016/j.cell.2013.12.019.

DOI:10.1016/j.cell.2013.12.019
PMID:24439369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3938284/
Abstract

Methylation of cytosines in the mammalian genome represents a key epigenetic modification and is dynamically regulated during development. Compelling evidence now suggests that dynamic regulation of DNA methylation is mainly achieved through a cyclic enzymatic cascade comprised of cytosine methylation, iterative oxidation of methyl group by TET dioxygenases, and restoration of unmodified cytosines by either replication-dependent dilution or DNA glycosylase-initiated base excision repair. In this review, we discuss the mechanism and function of DNA demethylation in mammalian genomes, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes.

摘要

哺乳动物基因组中的胞嘧啶甲基化是一种关键的表观遗传修饰，并且在发育过程中受到动态调控。现在有强有力的证据表明，DNA 甲基化的动态调控主要是通过一个由胞嘧啶甲基化、TET 双加氧酶对甲基的反复氧化以及复制依赖性稀释或 DNA 糖苷酶起始的碱基切除修复来恢复未修饰的胞嘧啶组成的循环酶促级联来实现的。在这篇综述中，我们讨论了哺乳动物基因组中 DNA 去甲基化的机制和功能，特别关注了在各种生物过程中，胞嘧啶修饰途径的发育调节是如何与 DNA 甲基化的主动逆转偶联的。

相似文献

[1]
Reversing DNA methylation: mechanisms, genomics, and biological functions.

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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本文引用的文献

[1]
Cell cycle-dependent turnover of 5-hydroxymethyl cytosine in mouse embryonic stem cells.

PLoS One. 2013-12-10

[2]
Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation.

Cell. 2013-12-5

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Nature. 2013-12-1

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Nucleic Acids Res. 2013-11-7

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Mol Cell. 2013-11-7

[6]
Vitamin C modulates TET1 function during somatic cell reprogramming.

Nat Genet. 2013-10-27

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A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation.

Genome Biol. 2013

[8]
TET enzymes, TDG and the dynamics of DNA demethylation.

Nature. 2013-10-24

[9]
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Nat Biotechnol. 2013-10-9

[10]
Tet1 is critical for neuronal activity-regulated gene expression and memory extinction.

Neuron. 2013-9-18

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