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Engineered Split-TET2 Enzyme for Inducible Epigenetic Remodeling

Author:
Lee, Minjung, Li, Jia, Liang, Yi, Ma, Guolin, Zhang, Jixiang, He, Lian, Liu, Yuliang, Li, Qian, Li, Minyong, Sun, Deqiang, Zhou, Yubin, Huang, Yun
Source:
Journal of the American Chemical Society 2017 v.139 no.13 pp. 4659-4662
ISSN:
1520-5126
Subject:
DNA, chromatin, epigenetics, genetic code, genome, mammals, oxidation
Abstract:
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.
Agid:
5662156