1. Different roles for Tet1 and Tet2 proteins in reprogramming-mediated erasure of imprints induced by EGC fusion.
- Author
-
Piccolo FM, Bagci H, Brown KE, Landeira D, Soza-Ried J, Feytout A, Mooijman D, Hajkova P, Leitch HG, Tada T, Kriaucionis S, Dawlaty MM, Jaenisch R, Merkenschlager M, and Fisher AG
- Subjects
- 5-Methylcytosine analogs & derivatives, Animals, B-Lymphocytes cytology, Base Sequence, Cell Line, Cytosine analogs & derivatives, Cytosine metabolism, DNA Methylation, Dioxygenases, Embryonic Stem Cells cytology, Gene Expression, Germ Cells cytology, Green Fluorescent Proteins biosynthesis, Humans, Insulin-Like Growth Factor II genetics, Mice, Molecular Sequence Data, Octamer Transcription Factor-3 genetics, Octamer Transcription Factor-3 metabolism, Polymorphism, Single Nucleotide, Proteins genetics, Proteins metabolism, RNA, Long Noncoding genetics, Sequence Analysis, DNA, Cell Fusion, DNA-Binding Proteins physiology, Genomic Imprinting, Proto-Oncogene Proteins physiology
- 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF