Active DNA demethylation in human postmitotic cells correlates with activating histone modifications, but not transcription levels.
Active DNA demethylation in human postmitotic cells correlates with activating histone modifications, but not transcription levels.
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DOI：
10.1186/gb-2010-11-6-r63
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发表时间：
2010
期刊：
影响因子：
12.3
通讯作者：
Rehli M
中科院分区：
文献类型：
--
作者：
Klug M;Heinz S;Gebhard C;Schwarzfischer L;Krause SW;Andreesen R;Rehli M
在哺乳动物中，DNA甲基化的动力学，特别是胞嘧啶甲基化的调节性主动去除，仍然是一个谜，部分原因是缺乏适当的模型系统来研究DNA去甲基化。以前的工作主要集中在增殖的细胞类型，有丝分裂阻滞使用药理学抑制剂，以区分主动和被动的DNA去甲基化机制。我们在有丝分裂后细胞的自然环境中探索了这种表观遗传现象：人外周血单核细胞分化为巨噬细胞或树突状细胞，其在没有细胞分裂的情况下进行。使用一个全球性的，比较CpG甲基化分析方法，我们确定了许多新的例子，积极的DNA去甲基化和特点伴随的转录和表观遗传事件在这些网站在单核细胞分化。我们发现，主动DNA去甲基化并不局限于近端启动子，并且去甲基化的时间过程因单个CpG而异。不管它们的位置，甲基化胞嘧啶的去除总是与激活组蛋白标记的出现相一致。脱甲基化事件在来自不同个体的单核细胞衍生的树突状细胞中是高度可重复的。我们的数据表明，主动DNA去甲基化是一个精确的目标事件，平行或遵循组蛋白的修饰，但不一定耦合到转录活性的改变。
In mammals, the dynamics of DNA methylation, in particular the regulated, active removal of cytosine methylation, has remained a mystery, partly due to the lack of appropriate model systems to study DNA demethylation. Previous work has largely focused on proliferating cell types that are mitotically arrested using pharmacological inhibitors to distinguish between active and passive mechanisms of DNA demethylation. We explored this epigenetic phenomenon in a natural setting of post-mitotic cells: the differentiation of human peripheral blood monocytes into macrophages or dendritic cells, which proceeds without cell division. Using a global, comparative CpG methylation profiling approach, we identified many novel examples of active DNA demethylation and characterized accompanying transcriptional and epigenetic events at these sites during monocytic differentiation. We show that active DNA demethylation is not restricted to proximal promoters and that the time-course of demethylation varies for individual CpGs. Irrespective of their location, the removal of methylated cytosines always coincided with the appearance of activating histone marks. Demethylation events are highly reproducible in monocyte-derived dendritic cells from different individuals. Our data suggest that active DNA demethylation is a precisely targeted event that parallels or follows the modification of histones, but is not necessarily coupled to alterations in transcriptional activity.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
影响因子：
4.5
作者：
Jin SG;Guo C;Pfeifer GP
通讯作者：
Pfeifer GP
DOI：
10.1016/j.biocel.2007.02.006
发表时间：
2007-01-01
影响因子：
4
作者：
Ivascu, Claudia;Wasserkort, Reinhold;Eckhardt, Florian
通讯作者：
Eckhardt, Florian
影响因子：
4.8
作者：
JOST, JP;SIEGMANN, M;LEUNG, R
通讯作者：
LEUNG, R
DOI：
10.1073/pnas.90.10.4684
发表时间：
1993-05-15
影响因子：
11.1
作者：
JOST, JP
通讯作者：
JOST, JP