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      X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo.

      Nature genetics
      Animals, Dosage Compensation, Genetic, Embryonic and Fetal Development, genetics, Female, Gene Expression, Genetic Linkage, Gestational Age, In Vitro Techniques, Lac Operon, Mice, Mice, Transgenic, Organ Specificity, Pregnancy, X Chromosome, beta-Galactosidase

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          Abstract

          During mammalian development, one of the two X chromosomes in female embryos is randomly inactivated in the somatic cell in order to achieve gene dosage compensation. But is X inactivation established simultaneously or is it accomplished over time in a lineage-dependent fashion? We have examined this question in mouse embryos carrying an X-linked lacZ transgene. This transgene is subject to inactivation and the loss of beta-galactosidase activity provides a direct indication of X inactivation in individual cells. We find that X inactivation proceeds with different schedules in different somatic tissues, and the notochord, the heart, cranial mesoderm and the hindgut are among the last tissues to undergo X inactivation.

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          Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse.

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            Mammalian X-chromosome inactivation.

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              Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation.

              DNA sequences have previously been identified in the first intron of the mouse Hprt gene that are methylated on the inactive but not the active X chromosome. The temporal relationship between methylation of these sequences and X-inactivation was studied in teratocarcinoma cells and postimplantation mouse embryos: the sequences are unmethylated prior to X-inactivation and do not become methylated on the inactive X in most fetal cells until several days postinactivation. Such inactive X-specific methylation occurs in a significantly smaller proportion of the cells in the extra-embryonic tissues, yolk sac mesoderm and endoderm, than in the fetus. These data suggest that the inactive X-specific methylation of sequences such as those in the first intron of the Hprt gene does not play any role in the primary events of X-inactivation, but may function as part of a secondary, tissue-specific mechanism for maintaining the inactive state.
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