Engineered Split-TET2 Enzyme for Inducible Epigenetic Remodeling.
Engineered Split-TET2 Enzyme for Inducible Epigenetic Remodeling.
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DOI：
10.1021/jacs.7b01459
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发表时间：
2017-04-05
影响因子：
15
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Lee M;Li J;Liang Y;Ma G;Zhang J;He L;Liu Y;Li Q;Li M;Sun D;Zhou Y;Huang Y
5-甲基胞嘧啶（5 mC）双加氧酶的十-十一易位（泰特）家族催化5 mC转化为5-羟甲基胞嘧啶（5 hmC）并进一步氧化物质以促进活性DNA去甲基化。在这里，我们设计了一种分裂TET 2酶，使哺乳动物细胞中的5 mC氧化和随后的表观遗传状态重塑的时间控制。我们进一步证明了使用这种化学诱导系统来剖析哺乳动物基因组中DNA羟甲基化和染色质可及性之间的相关性。这种化学诱导的表观基因组重塑工具将在不改变遗传密码的情况下在询问细胞系统以及在探测各种生物系统中的表观基因型-表型关系中找到广泛的用途。
The Ten-eleven translocation (TET) family of 5-methylcytosine (5mC) dioxygenases catalyze the conversion of 5mC into 5-hydroxymethylcytosine (5hmC) and further oxidized species to promote active DNA demethylation. Here we engineered a split-TET2 enzyme to enable temporal control of 5mC oxidation and subsequent remodeling of epigenetic states in mammalian cells. We further demonstrate the use of this chemically inducible system to dissect the correlation between DNA hydroxymethylation and chromatin accessibility in the mammalian genome. This chemical-inducible epigenome remodeling tool will find broad use in interrogating cellular systems without altering the genetic code, as well as in probing the epigenotype–phenotype relations in various biological systems.