5-Hydroxymethylcytosine--the elusive epigenetic mark in mammalian DNA.
5-Hydroxymethylcytosine--the elusive epigenetic mark in mammalian DNA.
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DOI：
10.1039/c2cs35104h
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发表时间：
2012-11-07
影响因子：
46.2
通讯作者：
Klimašauskas S
中科院分区：
文献类型：
--
作者：
Kriukienė E;Liutkevičiūtė Z;Klimašauskas S
在过去的十年里，表观遗传现象声称在细胞调控过程中发挥了核心作用，并被证明是理解复杂的人类疾病的重要因素。最被理解的表观遗传机制之一是DNA甲基化。在哺乳动物基因组中，胞嘧啶(C)存在于两种功能状态：未甲基化或嘧啶环5位甲基化(5mC)。最近对人类和小鼠脑、神经元和小鼠胚胎干细胞基因组DNA的研究发现，CpG二核苷酸中相当大一部分5mC在Tet家族依赖于2-氧代戊二酸和Fe(II)的加氧酶的作用下转化为5-羟甲基胞嘧啶(HMC)。这些发现为长期难以捉摸的活性DNA去甲基化机制提供了重要线索，并支持了哺乳动物表观遗传调控领域的新一轮研究。这篇综述致力于对最流行的技术在哺乳动物基因组中分析HMC的适用性进行批判性评估。它还讨论了DNA中这个核苷酸碱基的形成和进一步转化的生化和化学方面的最新数据，以及它在细胞分化、胚胎发育和脑功能中可能的生物学作用。
Over the past decade, epigenetic phenomena claimed a central role in cell regulatory processes and proved important factors for understanding complex human diseases. One of the best understood epigenetic mechanisms is DNA methylation. In the mammalian genome, cytosines (C) were long known to exist in two functional states: unmethylated or methylated at the 5-position of the pyrimidine ring (5mC). Recent studies of genomic DNA from the human and mouse brain, neurons and from mouse embryonic stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethyl-cytosine (hmC) by the action of 2-oxoglutarate- and Fe(II)-dependent oxygenases of the TET family. These findings provided important clues in a long elusive mechanism of active DNA demethylation and bolstered a fresh wave of studies in the area of epigenetic regulation in mammals. This review is dedicated to critical assessment of the most popular techniques with respect to their suitability for analysis of hmC in mammalian genomes. It also discusses the most recent data on biochemical and chemical aspects of the formation and further conversion of this nucleobase in DNA and its possible biological roles in cell differentiation, embryogenesis and brain function.
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影响因子：
23.9
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
14.9
作者：
Jin SG;Kadam S;Pfeifer GP
通讯作者：
Pfeifer GP
影响因子：
64.5
作者：
Bhutani N;Burns DM;Blau HM
通讯作者：
Blau HM
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T