Interaction between the Xce locus and imprinting of the paternal X chromosome in mouse yolk-sac endoderm.

In female eutherian mammals preferential inactivation of the paternally derived X chromosome (XP) takes place in certain extra-embryonic tissues such as mouse yolk-sac endoderm, chorionic ectoderm and trophoblast and has been demonstrated both biochemically and cytologically. This is thought to be due to the paternal X chromosome being 'imprinted', that is, somehow marked as different, during either male gametogenesis or fertilization, causing primary nonrandom X-inactivation in tissues that differentiate early, such as trophectoderm and primitive endoderm, from which yolk-sac endoderm is derived. Different alleles of the X-chromosome controlling element, Xce locus, centrally located on the mouse X chromosome, also cause primary nonrandom X-chromosome inactivation in embryonic tissues which would otherwise show random inactivation. The work reported here was designed to elucidate whether the nonrandom inactivation of the imprinted XP in yolk-sac endoderm could be modified, or even overridden, by the effect of different Xce alleles. Using the modified Kanda method we have therefore studied the proportion of cells at metaphase with the XP inactive in separated yolk-sac endoderm and mesoderm of mouse embryos heterozygous for a marker X chromosome (Cattanach's translocation) carrying different Xce alleles on XP and XM. The results show that the extreme Xcec allele, when present on the paternally derived X, can significantly reduce the proportion of inactive XP seen in yolk-sac endoderm compared with controls. This is the first evidence that imprinting of XP is not an 'all or none' event but can be modified by a 'strong' allele at the Xce locus, and is another indication that the Xce locus may represent the inactivation centre.