Differential Regulation of Ten-Eleven Translocation Family of Dioxygenases by O-Linked {beta}-N-Acetylglucosamine Transferase OGT [Gene Regulation]

January 6th, 2014 by Zhang, Q., Liu, X., Gao, W., Li, P., Hou, J., Li, J., Wong, J.

Ten-Eleven Translocation family of dioxygenases (TET1/2/3) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) 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-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is not only a major TET3-interacting protein but also regulates TET3 subcellular localization and enzymatic activity. OGT catalyzes O-GlcNAcylation of TET3 and promotes TET3 nuclear export and consequently inhibits the formation of 5hmC catalyzed by TET3. Although TET1 and TET2 also interact with and can be O-GlcNAcylated by OGT, neither their subcellular localization nor enzymatic activity is affected by OGT. Furthermore, we show that the nuclear localization and O-GlcNAcylation of TET3 are regulated by glucose metabolism. Together our study reveals differential regulation of TET family proteins by OGT and a novel link between glucose metabolism and DNA epigenetic modification.
  • Posted in Journal of Biological Chemistry, Publications
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