title: Engineered Split-TET2 Enzyme for Inducible Epigenetic Remodeling.
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.
authors.affiliation: 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.
authors.forename: Minjung
authors.initials: M
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Guolin
authors.initials: G
authors.lastname: Ma
authors.affiliation: 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.|Department of Gastroenterology, Renmin Hospital of Wuhan University , Wuhan, Hubei 430060, China.
authors.forename: Jixiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lian
authors.initials: L
authors.lastname: He
authors.affiliation: 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.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shandong University , 44 Wenhua Road W., Jinan, Shandong 250012, China.
authors.forename: Minyong
authors.identifier: 0000-0003-3276-4921
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Yubin
authors.identifier: 0000-0001-7962-0517
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D044503:5-Methylcytosine / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D049308:Dioxygenases; D044127:Epigenesis, Genetic / Q000235:genetics*; D005815:Genetic Code / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D015202:Protein Engineering; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D044503:5-Methylcytosine; D049308:Dioxygenases; C541081:TET2 protein, human