Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 24 November 2000:
Vol. 290. no. 5496, pp. 1578 - 1581
DOI: 10.1126/science.290.5496.1578

Reports

X-Chromosome Inactivation in Cloned Mouse Embryos

Kevin Eggan,12* Hidenori Akutsu,3* Konrad Hochedlinger,1 William Rideout III,1 Ryuzo Yanagimachi,3 Rudolf Jaenisch12dagger

To study whether cloning resets the epigenetic differences between the two X chromosomes of a somatic female nucleus, we monitored X inactivation in cloned mouse embryos. Both X chromosomes were active during cleavage of cloned embryos, followed by random X inactivation in the embryo proper. In the trophectoderm (TE), X inactivation was nonrandom with the inactivated X of the somatic donor being chosen for inactivation. When female embryonic stem cells with two active X chromosomes were used as donors, random X inactivation was seen in the TE and embryo. These results demonstrate that epigenetic marks can be removed and reestablished on either X chromosome during cloning. Our results also suggest that the epigenetic marks imposed on the X chromosomes during gametogenesis, responsible for normal imprinted X inactivation in the TE, are functionally equivalent to the marks imposed on the chromosomes during 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.

dagger    To whom correspondence should be addressed. E-mail: jaenisch{at}wi.mit.edu


Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Induced Pluripotency of Mouse and Human Somatic Cells.
N. Maherali and K. Hochedlinger (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Dynamic Reprogramming of Histone Acetylation and Methylation in the First Cell Cycle of Cloned Mouse Embryos.
F. Wang, Z. Kou, Y. Zhang, and S. Gao (2007)
Biol Reprod 77, 1007-1016
   Abstract »    Full Text »    PDF »
Dosage compensation in mammals: fine-tuning the expression of the X chromosome.
E. Heard and C. M. Disteche (2006)
Genes & Dev. 20, 1848-1867
   Abstract »    Full Text »    PDF »
Embryonic stem-cell gametes: the new frontier in human reproduction.
Z. Master (2006)
Hum. Reprod. 21, 857-863
   Abstract »    Full Text »    PDF »
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.
R. K. Ng and J. B. Gurdon (2005)
PNAS 102, 1957-1962
   Abstract »    Full Text »    PDF »
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.
J. B. Gurdon and J. A. Byrne (2003)
PNAS 100, 8048-8052
   Abstract »    Full Text »    PDF »
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.
W. Reik, W. Dean, and J. Walter (2001)
Science 293, 1089-1093
   Abstract »    Full Text »    PDF »
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.
M. A. Larson, K. Kimura, H. M. Kubisch, and R. M. Roberts (2001)
PNAS
   Abstract »    Full Text »    PDF »
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 »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)