title: Ten-eleven translocation 1 (Tet1) is regulated by O-linked N-acetylglucosamine transferase (Ogt) for target gene repression in mouse embryonic stem cells.
abstract: As a member of the Tet (Ten-eleven translocation) family proteins that can convert 5-methylcytosine (5mC) to 5-hydroxylmethylcytosine (5hmC), Tet1 has been implicated in regulating global DNA demethylation and gene expression. Tet1 is highly expressed in embryonic stem (ES) cells and appears primarily to repress developmental genes for maintaining pluripotency. To understand how Tet1 may regulate gene expression, we conducted large scale immunoprecipitation followed by mass spectrometry of endogenous Tet1 in mouse ES cells. We found that Tet1 could interact with multiple chromatin regulators, including Sin3A and NuRD complexes. In addition, we showed that Tet1 could also interact with the O-GlcNAc transferase (Ogt) and be O-GlcNAcylated. Depletion of Ogt led to reduced Tet1 and 5hmC levels on Tet1-target genes, whereas ectopic expression of wild-type but not enzymatically inactive Ogt increased Tet1 levels. Mutation of the putative O-GlcNAcylation site on Tet1 led to decreased O-GlcNAcylation and level of the Tet1 protein. Our results suggest that O-GlcNAcylation can positively regulate Tet1 protein concentration and indicate that Tet1-mediated 5hmC modification and target repression is controlled by Ogt.
authors.affiliation: the Verna and Marrs Department of Biochemistry and Molecular Biology and.
authors.forename: Feng-Tao
authors.initials: FT
authors.lastname: Shi
authors.affiliation: the Verna and Marrs Department of Biochemistry and Molecular Biology and.
authors.forename: Hyeung
authors.initials: H
authors.lastname: Kim
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China 510275 and.
authors.forename: Weisi
authors.initials: W
authors.lastname: Lu
authors.affiliation: the Verna and Marrs Department of Biochemistry and Molecular Biology and.
authors.forename: Quanyuan
authors.initials: Q
authors.lastname: He
authors.affiliation: the Verna and Marrs Department of Biochemistry and Molecular Biology and.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Goodell
authors.affiliation: the Verna and Marrs Department of Biochemistry and Molecular Biology and. Electronic address: mw6@bcm.edu.
authors.forename: Ma
authors.initials: M
authors.lastname: Wan
authors.affiliation: the Verna and Marrs Department of Biochemistry and Molecular Biology and; From the Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China 510275 and. Electronic address: songyang@bcm.edu.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental; D006031:Glycosylation; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C540839:TET1 protein, mouse; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
keywords: DNA Methylation; Embryonic Stem Cell; Epigenetics; Posttranslational Modification; Stem Cells