Engineered Split-TET2 Enzyme for Inducible Epigenetic Remodeling

• DOI: 10.1021/jacs.7b01459
• Publication Date: 2017-03-15T15:51:06Z
• Authors: Minjung Lee; Jia Li; Yi Liang; Guolin Ma; Jixiang Zhang; Lian He; Yuliang Liu; Qian Li; Minyong Li; Deqiang Sun; Yubin Zhou; Yun Huang
• Keywords: 0301 basic medicine; Models, Genetic; Protein Engineering; Dioxygenases; Epigenesis, Genetic; DNA-Binding Proteins; 03 medical and health sciences; HEK293 Cells; Genetic Code; Proto-Oncogene Proteins; 5-Methylcytosine; Humans; HeLa Cells

The Ten-eleven translocation (TET) family of 5-methylcytosine (5mC) dioxygenases catalyze the conversion 5mC into 5-hydroxymethylcytosine (5hmC) and further oxidized species to promote active DNA demethylation. Here we engineered a split-TET2 enzyme enable temporal control oxidation subsequent remodeling epigenetic states in mammalian cells. We demonstrate use this chemically inducible system dissect correlation between hydroxymethylation chromatin accessibility genome. This chemical-inducible epigenome tool will find broad interrogating cellular systems without altering genetic code, as well probing epigenotype-phenotype relations various biological systems.