title: Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked β-N-acetylglucosamine transferase (OGT).
abstract: The ten-eleven translocation (TET) family of dioxygenases (TET1/2/3) converts 5-methylcytosine to 5-hydroxymethylcytosine and provides a vital mechanism for DNA demethylation. However, how TET proteins are regulated is largely unknown. Here we report that the O-linked β-GlcNAc (O-GlcNAc) transferase (OGT) is not only a major TET3-interacting protein but also regulates TET3 subcellular localization and enzymatic activity. OGT catalyzes the O-GlcNAcylation of TET3, promotes TET3 nuclear export, and, consequently, inhibits the formation of 5-hydroxymethylcytosine catalyzed by TET3. Although TET1 and TET2 also interact with and can be O-GlcNAcylated by OGT, neither their subcellular localization nor their enzymatic activity are affected by OGT. Furthermore, we show that the nuclear localization and O-GlcNAcylation of TET3 are regulated by glucose metabolism. Our study reveals the differential regulation of TET family proteins by OGT and a novel link between glucose metabolism and DNA epigenetic modification.
authors.affiliation: From the Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China and.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
authors.forename: Wenqi
authors.initials: W
authors.lastname: Gao
authors.forename: Pishun
authors.initials: P
authors.lastname: Li
authors.forename: Jingli
authors.initials: J
authors.lastname: Hou
authors.forename: Jiwen
authors.initials: J
authors.lastname: Li
authors.forename: Jiemin
authors.initials: J
authors.lastname: Wong
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; D017351:N-Acetylglucosaminyltransferases; D005947:Glucose
keywords: DNA Methylation; Glucose Metabolism; Histone Modification; O-GlcNAcylation; Protein Export; TET3