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Originally published in Science Express on 11 December 2003
Science 30 January 2004:
Vol. 303. no. 5658, pp. 644 - 649
DOI: 10.1126/science.1092727
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Research Articles

Epigenetic Dynamics of Imprinted X Inactivation During Early Mouse Development

Ikuhiro Okamoto,1 Arie P. Otte,2 C. David Allis,3 Danny Reinberg,4 Edith Heard1*

The initiation of X-chromosome inactivation is thought to be tightly correlated with early differentiation events during mouse development. Here, we show that although initially active, the paternal X chromosome undergoes imprinted inactivation from the cleavage stages, well before cellular differentiation. A reversal of the inactive state, with a loss of epigenetic marks such as histone modifications and polycomb proteins, subsequently occurs in cells of the inner cell mass (ICM), which give rise to the embryo-proper in which random X inactivation is known to occur. This reveals the remarkable plasticity of the X-inactivation process during preimplantation development and underlines the importance of the ICM in global reprogramming of epigenetic marks in the early embryo.

1 CNRS UMR218, Curie Institute, 26 rue d'Ulm, Paris 75005, France.
2 Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, Netherlands.
3 Rockefeller University, Box 78, 1230 York Avenue, New York, NY 10021, USA.
4 Department of Biochemistry, Division of Nucleic Acids Enzymology, Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

* To whom correspondence should be addressed. E-mail: edith.heard{at}curie.fr

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