Journal
MOLECULAR CELL
Volume 49, Issue 6, Pages 1023-1033Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2013.01.032
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Funding
- Medical Research Council (MRC), UK
- European Research Council
- MRC centenary award
- Grants-in-Aid for Scientific Research [23390067] Funding Source: KAKEN
- Medical Research Council [MC_U120081295, MC_U120092689, MC_U120027516] Funding Source: researchfish
- MRC [MC_U120092689, MC_U120081295, MC_U120027516] Funding Source: UKRI
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Genonnic 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 (EGG) 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.
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