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

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 soma...

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Main Authors: Piccolo, Francesco M., Bagci, Hakan, Brown, Karen E., Landeira, David, Soza-Ried, Jorge, Feytout, Amelie, Mooijman, Dylan, Hajkova, Petra, Leitch, Harry G., Tada, Takashi, Kriaucionis, Skirmantas, Dawlaty, Meelad M., Jaenisch, Rudolf, Merkenschlager, Matthias, Fisher, Amanda G.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2013
Online Access:http://hdl.handle.net/1721.1/82160
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author Piccolo, Francesco M.
Bagci, Hakan
Brown, Karen E.
Landeira, David
Soza-Ried, Jorge
Feytout, Amelie
Mooijman, Dylan
Hajkova, Petra
Leitch, Harry G.
Tada, Takashi
Kriaucionis, Skirmantas
Dawlaty, Meelad M.
Jaenisch, Rudolf
Merkenschlager, Matthias
Fisher, Amanda G.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Piccolo, Francesco M.
Bagci, Hakan
Brown, Karen E.
Landeira, David
Soza-Ried, Jorge
Feytout, Amelie
Mooijman, Dylan
Hajkova, Petra
Leitch, Harry G.
Tada, Takashi
Kriaucionis, Skirmantas
Dawlaty, Meelad M.
Jaenisch, Rudolf
Merkenschlager, Matthias
Fisher, Amanda G.
author_sort Piccolo, Francesco M.
collection MIT
description 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.
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spelling mit-1721.1/821602022-10-01T02:30:08Z Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion Piccolo, Francesco M. Bagci, Hakan Brown, Karen E. Landeira, David Soza-Ried, Jorge Feytout, Amelie Mooijman, Dylan Hajkova, Petra Leitch, Harry G. Tada, Takashi Kriaucionis, Skirmantas Dawlaty, Meelad M. Jaenisch, Rudolf Merkenschlager, Matthias Fisher, Amanda G. Massachusetts Institute of Technology. Department of Biology Jaenisch, Rudolf 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. 2013-11-18T16:19:01Z 2013-11-18T16:19:01Z 2013-02 2012-11 Article http://purl.org/eprint/type/JournalArticle 10972765 http://hdl.handle.net/1721.1/82160 Piccolo, Francesco M., Hakan Bagci, Karen E. Brown, David Landeira, Jorge Soza-Ried, Amelie Feytout, Dylan Mooijman, et al. “Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion.” Molecular Cell 49, no. 6 (March 2013): 1023-1033. © 2013 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.molcel.2013.01.032 Molecular Cell Article is available under a Creative Commons license. http://creativecommons.org/ application/pdf Elsevier PMC
spellingShingle Piccolo, Francesco M.
Bagci, Hakan
Brown, Karen E.
Landeira, David
Soza-Ried, Jorge
Feytout, Amelie
Mooijman, Dylan
Hajkova, Petra
Leitch, Harry G.
Tada, Takashi
Kriaucionis, Skirmantas
Dawlaty, Meelad M.
Jaenisch, Rudolf
Merkenschlager, Matthias
Fisher, Amanda G.
Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion
title Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion
title_full Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion
title_fullStr Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion
title_full_unstemmed Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion
title_short Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion
title_sort different roles for tet1 and tet2 proteins in reprogramming mediated erasure of imprints induced by egc fusion
url http://hdl.handle.net/1721.1/82160
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