title: Differential regulation of genomic imprinting by TET proteins in embryonic stem cells.
abstract: TET proteins have been found to play an important role in active demethylation at CpG sites in mammals. There are some reports implicating their functions in removal of DNA methylation imprint at the imprinted regions in the germline. However, it is not well established whether TET proteins can also be involved in demethylation of DNA methylation imprint in embryonic stem (ES) cells. Here we report that loss of TET proteins caused a significant increase in DNA methylation at the Igf2-H19 imprinted region in ES cells. We also observed a variable increase in DNA methylation at the Peg1 imprinted region in the ES clones devoid of TET proteins, in particular in the differentiated ES cells. By contrast, we did not observe a significant increase of DNA methylation imprint at the Peg3, Snrpn and Dlk1-Dio3 imprinted regions in ES cells lacking TET proteins. Interestingly, loss of TET proteins did not result in a significant increase of DNA methylation imprint at the Igf2-H19 and Peg1 imprinted regions in the embryoid bodies (EB). Therefore, TET proteins seem to be differentially involved in maintaining DNA methylation imprint at a subset of imprinted regions in ES cells and EBs.
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Black Family Stem Cell Institute, Department of Oncological Sciences, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Mao
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Black Family Stem Cell Institute, Department of Oncological Sciences, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Ray
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Black Family Stem Cell Institute, Department of Oncological Sciences, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Black Family Stem Cell Institute, Department of Oncological Sciences, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Fong T
authors.initials: FT
authors.lastname: Bell
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Black Family Stem Cell Institute, Department of Oncological Sciences, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Ng
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xu
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Black Family Stem Cell Institute, Department of Oncological Sciences, Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: xiajun.li@mssm.edu.
authors.forename: Xiajun
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D049308:Dioxygenases; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics; D051379:Mice; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D055517:snRNP Core Proteins / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C512925:Dlk1 protein, mouse; C094335:H19 long non-coding RNA; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D062085:RNA, Long Noncoding; C540839:TET1 protein, mouse; C103637:mesoderm specific transcript protein; D055517:snRNP Core Proteins; D007335:Insulin-Like Growth Factor II; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D049308:Dioxygenases; C551914:Tet2 protein, mouse; C551915:Tet3 protein, mouse
keywords: Bisulfite sequencing; COBRA analysis; DNA methylation; EB; ES cells; Genomic imprinting; TET