Epigenetic Dynamics of Imprinted X Inactivation During Early Mouse Development

Author:

Okamoto Ikuhiro1234,Otte Arie P.1234,Allis C. David1234,Reinberg Danny1234,Heard Edith1234

Affiliation:

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.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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