During development of the female mouse embryo, one of the two X chromosomes is inactivated in a random manner in most cell lineages1. However, in the extraembryonic trophectoderm and primary endoderm lineages there is preferential inactivation of the paternally derived X chromosome2-4. The inactivated X chromosomes of the extraembryonic and somatic tissues appear equally inactive at the level of the expression of X-linked genes2-7. However, there are differences in the timing of their replication 8-10 and the extent of DNA modification as determined by gene transfer11-15. The identification of transgenic animals carrying X-linked modified α-fetoprotein (AFP) genes allowed us to examine whether the inactivation process extends to an autosomal gene which is normally expressed at high levels in specific extraembryonic and somatic cells, and if so, whether the inactivation process is different in these two tissues. Our results demonstrate that the X-linked AFP genes were expressed on the inactive X chromosome in the visceral endoderm of the yolk sac but not in fetal liver. Thus, the transcriptional activity of the AFP minigene on the inactive X chromosome is dependent on the tissue in which it resides, and most probably reflects differences in the nature of the maintenance of the inactive state of the extraembryonic and embryonic X chromosomes.
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