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

doi:10.1016/j.molcel.2013.01.032

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 journal › Article › peer-review

87 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 language	English (US)
Pages (from-to)	1023-1033
Number of pages	11
Journal	Molecular Cell
Volume	49
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2013.01.032
State	Published - Mar 28 2013
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.molcel.2013.01.032

Cite this

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

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 & Fisher, AG 2013, 'Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion', Molecular Cell, vol. 49, no. 6, pp. 1023-1033. https://doi.org/10.1016/j.molcel.2013.01.032

@article{1029e5c35a574c48b0099ef70a835c8b,

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.",

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

note = "Funding Information: We thank C.F. Pereira for help and discussions, H. Mira-Bontenbal and I. Ferreiros-Vidal for assistance in the derivation of the 2rB cells, and T. Carr and members of the Clinical Sciences Center FACS facility for advice and technical support. This work was funded by the Medical Research Council (MRC), UK (K.E.B., M.M., and A.G.F.), the European Research Council (J.S.-R.), and an MRC centenary award (F.M.P.). ",

year = "2013",

month = mar,

day = "28",

doi = "10.1016/j.molcel.2013.01.032",

language = "English (US)",

volume = "49",

pages = "1023--1033",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion

AU - Piccolo, Francesco M.

AU - Bagci, Hakan

AU - Brown, Karen E.

AU - Landeira, David

AU - Soza-Ried, Jorge

AU - Feytout, Amelie

AU - Mooijman, Dylan

AU - Hajkova, Petra

AU - Leitch, Harry G.

AU - Tada, Takashi

AU - Kriaucionis, Skirmantas

AU - Dawlaty, Meelad M.

AU - Jaenisch, Rudolf

AU - Merkenschlager, Matthias

AU - Fisher, Amanda G.

N1 - Funding Information: We thank C.F. Pereira for help and discussions, H. Mira-Bontenbal and I. Ferreiros-Vidal for assistance in the derivation of the 2rB cells, and T. Carr and members of the Clinical Sciences Center FACS facility for advice and technical support. This work was funded by the Medical Research Council (MRC), UK (K.E.B., M.M., and A.G.F.), the European Research Council (J.S.-R.), and an MRC centenary award (F.M.P.).

PY - 2013/3/28

Y1 - 2013/3/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84875783959&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875783959&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2013.01.032

DO - 10.1016/j.molcel.2013.01.032

M3 - Article

C2 - 23453809

AN - SCOPUS:84875783959

SN - 1097-2765

VL - 49

SP - 1023

EP - 1033

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this