Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster.
Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster.
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DOI：
10.1038/ncomms1826
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发表时间：
2012-05-08
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
分化伴随着广泛的表观基因组重编程，导致茎秆因子的抑制和激活的谱系特异性基因的转录维持。在这里，我们使用哺乳动物发育基因的Hoxa集群作为模型系统来跟踪维甲酸诱导分化过程中DNA修饰模式的变化。我们发现不活跃的簇被5-甲基胞嘧啶（5mC）的定义模式所标记。诱导分化后，簇的活性前部逐渐富集5-羟甲基胞嘧啶（5hmC），与基因阵列的共线激活模式密切相关，与5mC的减少是平行的。5hmC生成双加氧酶Tet2的耗竭会损害Hoxa活性的维持，并部分恢复5mC水平。我们的研究结果表明，Tet2基因特异性5mC-5hmC转化对于维持谱系特异性位点的活性染色质状态至关重要。
Differentiation is accompanied by extensive epigenomic reprogramming, leading to the repression of stemness factors and the transcriptional maintenance of activated lineage-specific genes. Here we use the mammalian Hoxa cluster of developmental genes as a model system to follow changes in DNA modification patterns during retinoic acid induced differentiation. We find the inactive cluster to be marked by defined patterns of 5-methylcytosine (5mC). Upon the induction of differentiation, the active anterior part of the cluster becomes increasingly enriched in 5-hydroxymethylcytosine (5hmC), following closely the colinear activation pattern of the gene array, which is paralleled by the reduction of 5mC. Depletion of the 5hmC generating dioxygenase Tet2 impairs the maintenance of Hoxa activity and partially restores 5mC levels. Our results indicate that gene specific 5mC-5hmC conversion by Tet2 is crucial for the maintenance of active chromatin states at lineage-specific loci.
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影响因子：
4.5
作者：
Grönniger E;Weber B;Heil O;Peters N;Stäb F;Wenck H;Korn B;Winnefeld M;Lyko F
通讯作者：
Lyko F
影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
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
影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W
DOI：
10.1073/pnas.1018279108
发表时间：
2011-05-03
影响因子：
11.1
作者：
Kim, Yoon Jung;Cecchini, Katharine R.;Kim, Tae Hoon
通讯作者：
Kim, Tae Hoon