Epigenetic dynamics of imprinted X inactivation during early mouse development

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 inac-tivation from the cleavage stages, well before cellular differentiation. A reversal of the inactive state,with a loss of epigeneticmarks such as histonemodifications 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 preim-plantation development and underlines the importance of the ICM in global re-programming of epigenetic marks in the early embryo. In mammals, dosage compensation between XX females and XY males is achieved by inactivating one of the two X chromosomes during early female embryogenesis (1). Classi-cal biochemical and cytological analyses hav