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Kevin Eggan,12*Hidenori Akutsu,3*Konrad Hochedlinger,1William Rideout III,1Ryuzo Yanagimachi,3Rudolf Jaenisch12
To study whether cloning resets the epigenetic
differences between the two X chromosomes of a somatic female nucleus,
we monitoredX inactivation in cloned mouse embryos. Both X chromosomes
wereactive during cleavage of cloned embryos, followed by random Xinactivation in the embryo proper. In the trophectoderm (TE),X
inactivation was nonrandom with the inactivated X of the somaticdonor
being chosen for inactivation. When female embryonic stemcells with
two active X chromosomes were used as donors, randomX inactivation was
seen in the TE and embryo. These results demonstratethat epigenetic
marks can be removed and reestablished on eitherX chromosome during
cloning. Our results also suggest that theepigenetic marks imposed on
the X chromosomes during gametogenesis,responsible for normal
imprinted X inactivation in the TE, arefunctionally equivalent to the
marks imposed on the chromosomesduring somatic X inactivation.
1 Whitehead Institute for Biomedical Research
and
2 Department of Biology, Massachusetts Institute
of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
3 Department of Anatomy and Reproductive Biology,
John A. Burns School of Medicine, University of Hawaii, Honolulu, HI
96822, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
jaenisch{at}wi.mit.edu
Inheritable Histone H4 Acetylation of Somatic Chromatins in Cloned Embryos.
G. Wee, D.-B. Koo, B.-S. Song, J.-S. Kim, M.-J. Kang, S.-J. Moon, Y.-K. Kang, K.-K. Lee, and Y.-M. Han (2006)
J. Biol. Chem.
281, 6048-6057
|Abstract »|Full Text »|PDF »
Epigenetic reprogramming in mammals.
H. D. Morgan, F. Santos, K. Green, W. Dean, and W. Reik (2005)
Hum. Mol. Genet.
14, R47-R58
|Abstract »|Full Text »|PDF »
Epigenetic memory of active gene transcription is inherited through somatic cell nuclear transfer.
Aberrant Gene Expression in Organs of Bovine Clones That Die Within Two Days after Birth.
S. Li, Y. Li, W. Du, L. Zhang, S. Yu, Y. Dai, C. Zhao, and N. Li (2005)
Biol Reprod
72, 258-265
|Abstract »|Full Text »|PDF »
Epigenetic and Genomic Imprinting Analysis in Nuclear Transfer Derived Bos gaurus/Bos taurus Hybrid Fetuses.
S. V. Dindot, P. W. Farin, C. E. Farin, J. Romano, S. Walker, C. Long, and J. A. Piedrahita (2004)
Biol Reprod
71, 470-478
|Abstract »|Full Text »|PDF »
Epigenetic Dynamics of Imprinted X Inactivation During Early Mouse Development.
I. Okamoto, A. P. Otte, C. D. Allis, D. Reinberg, and E. Heard (2004)
Science
303, 644-649
|Abstract »|Full Text »|PDF »
Nuclear Cloning, Epigenetic Reprogramming, and Cellular Differentiation.
R. JAENISCH, K. HOCHEDLINGER, R. BLELLOCH, Y. YAMADA, K. BALDWIN, and K. EGGAN (2004)
Cold Spring Harb Symp Quant Biol
69, 19-28
|Abstract »|PDF »
Mammalian X-Chromosome Inactivation: An Epigenetics Paradigm.
E. HEARD, J. CHAUMEIL, O. MASUI, and I. OKAMOTO (2004)
Cold Spring Harb Symp Quant Biol
69, 89-102
|Abstract »|PDF »
Nuclear Transplantation, Embryonic Stem Cells, and the Potential for Cell Therapy.
K. Hochedlinger and R. Jaenisch (2003)
N. Engl. J. Med.
349, 275-286
|Full Text »|PDF »
The first half-century of nuclear transplantation.
Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei.
A. Bortvin, K. Eggan, H. Skaletsky, H. Akutsu, D. L. Berry, R. Yanagimachi, D. C. Page, and R. Jaenisch (2003)
Development
130, 1673-1680
|Abstract »|Full Text »|PDF »
Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells.
J. Lee, K. Inoue, R. Ono, N. Ogonuki, T. Kohda, T. Kaneko-Ishino, A. Ogura, and F. Ishino (2003)
Development
129, 1807-1817
|Abstract »|Full Text »|PDF »
Oct4 distribution and level in mouse clones: consequences for pluripotency.
M. Boiani, S. Eckardt, H. R. Scholer, and K. J. McLaughlin (2002)
Genes & Dev.
16, 1209-1219
|Abstract »|Full Text »|PDF »
In Vitro Production and Nuclear Transfer Affect Dosage Compensation of the X-Linked Gene Transcripts G6PD, PGK, and Xist in Preimplantation Bovine Embryos.
C. Wrenzycki, A. Lucas-Hahn, D. Herrmann, E. Lemme, K. Korsawe, and H. Niemann (2002)
Biol Reprod
66, 127-134
|Abstract »|Full Text »
Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos.
W. Dean, F. Santos, M. Stojkovic, V. Zakhartchenko, J. Walter, E. Wolf, and W. Reik (2001)
PNAS
98, 13734-13738
|Abstract »|Full Text »|PDF »
Epigenetic Reprogramming in Mammalian Development.
Nuclear Cloning and Epigenetic Reprogramming of the Genome.
W. M. Rideout III, K. Eggan, and R. Jaenisch (2001)
Science
293, 1093-1098
|Abstract »|Full Text »|PDF »
Sexual dimorphism among bovine embryos in their ability to make the transition to expanded blastocyst and in the expression of the signaling molecule IFN-tau.
Synergism of Xist Rna, DNA Methylation, and Histone Hypoacetylation in Maintaining X Chromosome Inactivation.
G. Csankovszki, A. Nagy, and R. Jaenisch (2001)
J. Cell Biol.
153, 773-784
|Abstract »|Full Text »|PDF »
Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation.
K. Eggan, H. Akutsu, J. Loring, L. Jackson-Grusby, M. Klemm, W. M. Rideout 3rd, R. Yanagimachi, and R. Jaenisch (2001)
PNAS
|Abstract »|Full Text »
Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation.
K. Eggan, H. Akutsu, J. Loring, L. Jackson-Grusby, M. Klemm, W. M. Rideout 3rd, R. Yanagimachi, and R. Jaenisch (2001)
PNAS
98, 6209-6214
|Abstract »|Full Text »|PDF »
Sexual dimorphism among bovine embryos in their ability to make the transition to expanded blastocyst and in the expression of the signaling molecule IFN-tau.
M. A. Larson, K. Kimura, H. M. Kubisch, and R. M. Roberts (2001)
PNAS
98, 9677-9682
|Abstract »|Full Text »|PDF »