Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion

Francesco M. Piccolo, Hakan Bagci, Karen E. Brown, David Landeira, Jorge Soza-Ried, Amelie Feytout, Dylan Mooijman, Petra Hajkova, Harry G. Leitch, Takashi Tada, Skirmantas Kriaucionis, Meelad M. Dawlaty, Rudolf Jaenisch, Matthias Merkenschlager, Amanda G. Fisher

Research output: Contribution to journalArticle

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1023-1033
Number of pages11
JournalMolecular Cell
Volume49
Issue number6
DOIs
StatePublished - Mar 28 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Piccolo, F. M., Bagci, H., Brown, K. E., Landeira, D., Soza-Ried, J., Feytout, A., Mooijman, D., Hajkova, P., Leitch, H. G., Tada, T., Kriaucionis, S., Dawlaty, M. M., Jaenisch, R., Merkenschlager, M., & Fisher, A. G. (2013). Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion. Molecular Cell, 49(6), 1023-1033. https://doi.org/10.1016/j.molcel.2013.01.032