title: Different roles for Tet1 and Tet2 proteins in reprogramming-mediated erasure of imprints induced by EGC fusion.
abstract: Genomic imprinting directs the allele-specific marking and expression of loci according to their parental origin. Differential DNA methylation at imprinted control regions (ICRs) is established in gametes and, although largely preserved through development, can be experimentally reset by fusing somatic cells with embryonic germ cell (EGC) lines. Here, we show that the Ten-Eleven Translocation proteins Tet1 and Tet2 participate in the efficient erasure of imprints in this model system. The fusion of B cells with EGCs initiates pluripotent reprogramming, in which rapid re-expression of Oct4 is accompanied by an accumulation of 5-hydroxymethylcytosine (5hmC) at several ICRs. Tet2 was required for the efficient reprogramming capacity of EGCs, whereas Tet1 was necessary to induce 5-methylcytosine oxidation specifically at ICRs. These data show that the Tet1 and Tet2 proteins have discrete roles in cell-fusion-mediated pluripotent reprogramming and imprint erasure in somatic cells.
authors: Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors: Francesco M
authors: FM
authors: Piccolo
authors: Hakan
authors: H
authors: Bagci
authors: Karen E
authors: KE
authors: Brown
authors: David
authors: D
authors: Landeira
authors: Jorge
authors: J
authors: Soza-Ried
authors: Amelie
authors: A
authors: Feytout
authors: Dylan
authors: D
authors: Mooijman
authors: Petra
authors: P
authors: Hajkova
authors: Harry G
authors: HG
authors: Leitch
authors: Takashi
authors: T
authors: Tada
authors: Skirmantas
authors: S
authors: Kriaucionis
authors: Meelad M
authors: MM
authors: Dawlaty
authors: Rudolf
authors: R
authors: Jaenisch
authors: Matthias
authors: M
authors: Merkenschlager
authors: Amanda G
authors: AG
authors: Fisher
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001483:Base Sequence; D002459:Cell Fusion; D002460:Cell Line; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology*; D049308:Dioxygenases; D053595:Embryonic Stem Cells / Q000166:cytology; D015870:Gene Expression; D018392:Genomic Imprinting; D005854:Germ Cells / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D062085:RNA, Long Noncoding; C540839:TET1 protein, mouse; C103637:mesoderm specific transcript protein; C011865:5-hydroxymethylcytosine; D049452:Green Fluorescent Proteins; D007335:Insulin-Like Growth Factor II; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; C551914:Tet2 protein, mouse