Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.
Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.
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DOI：
10.1016/j.cell.2011.03.022
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发表时间：
2011-04-29
期刊：
影响因子：
64.5
通讯作者：
Song H
中科院分区：
文献类型：
--
作者：
Guo JU;Su Y;Zhong C;Ming GL;Song H
胞嘧啶甲基化是哺乳动物基因组DNA的主要共价修饰，在转录调控中起重要作用。然而，酶促去除这种表观遗传标记的分子机制仍然难以捉摸。在这里，我们表明，5-甲基胞嘧啶（5 mC）羟化酶TET 1，通过转换5 mCs为5-羟甲基胞嘧啶（5 hmCs），促进哺乳动物细胞中的DNA去甲基化，通过一个过程，需要碱基切除修复途径。虽然12种已知的人DNA糖基化酶的表达单独地没有增强哺乳动物细胞中5 hmC的去除，但是胞苷脱氨酶的AID（活化诱导的脱氨酶）/APOBEC（载脂蛋白B mRNA编辑酶复合物）家族促进外源引入的和内源性5 hmC的去甲基化。此外，Tet 1和Apobec 1参与体内成年小鼠大脑齿状回神经元活动诱导的、区域特异性的、活性DNA去甲基化和随后的基因表达。我们的研究表明，TET 1诱导的氧化脱氨机制的主动DNA去甲基化在哺乳动物中。
Cytosine methylation is the major covalent modification of mammalian genomic DNA and plays important roles in transcriptional regulation. The molecular mechanism underlying the enzymatic removal of this epigenetic mark, however, remains elusive. Here we show that 5-methylcytosine (5mC) hydroxylase TET1, by converting 5mCs to 5-hydroxymethylcytosines (5hmCs), promotes DNA demethylation in mammalian cells through a process that requires the base-excision repair pathway. While expression of the 12 known human DNA glycosylases individually did not enhance removal of 5hmCs in mammal cells, demethylation of both exogenously introduced and endogenous 5hmCs is promoted by the AID (activation-induced deaminase)/APOBEC (apolipoprotein B mRNA-editing enzyme complex) family of cytidine deaminases. Furthermore, Tet1 and Apobec1 are involved in neuronal activity-induced, region-specific, active DNA demethylation and subsequent gene expression in the dentate gyrus of the adult mouse brain in vivo. Our study suggests a TET1-induced oxidation-deamination mechanism for active DNA demethylation in mammals.
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影响因子：
14.9
作者：
Jin SG;Kadam S;Pfeifer GP
通讯作者：
Pfeifer GP
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
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping
影响因子：
4.8
作者：
Boorstein, RJ;Cummings, A;Teebor, GW
通讯作者：
Teebor, GW
DOI：
10.1126/science.1191078
发表时间：
2010-10-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bonasio R;Tu S;Reinberg D
通讯作者：
Reinberg D