Centre for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University , 2121 W Holcombe Boulevard, Houston, Texas 77030, United States.
Centre for Translational Cancer Research, Institute of Biosciences and Technology, Department of Medical Physiology, College of Medicine, Texas A&M University , 2121 W Holcombe Boulevard, Houston, Texas 77030, United States.
J Am Chem Soc. 2017 Apr 5;139(13):4659-4662. doi: 10.1021/jacs.7b01459. Epub 2017 Mar 23.
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.
TET 家族的 10-11 易位（TET）是 5-甲基胞嘧啶（5mC）双加氧酶，可催化 5mC 转化为 5-羟甲基胞嘧啶（5hmC）和进一步的氧化产物，从而促进活性 DNA 去甲基化。在这里，我们设计了一种分裂 TET2 酶，以实现对 5mC 氧化的时间控制，以及随后在哺乳动物细胞中重塑表观遗传状态。我们进一步证明了该化学诱导系统可用于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广泛用于研究不改变遗传密码的细胞系统，以及探究各种生物系统中的表型-表型关系。
