X-CHROMOSOME IMPRINTING AND INACTIVATION IN THE EARLY MAMMALIAN EMBRYO

Quantitative differences in X-linked gene expression between androgene tic (two paternal genomes), gynogenetic (two maternal genomes) and nor mal embryos provide clues into the roles of genomic imprinting and the X: autosome ratio in controlling X chromosome function during develop ment. These data and many others can be accounted for by a new model o f X-chromosome-inactivation (XCI). Expression of the Xist RNA from all paternal X chromosomes during development preimplantation leads to re pression of genes near the X-chromosome-inactivation center (Xic). Oth er genes are repressed as a result of spreading of the inactivation, b ut only in embryos with a least two X chromosomes. XY androgenones are only defieient in expression of genes near the Xic and can form blast ocysts, whereas XX androgenones completely inactivate both X chromosom es and die before the blastocyst stage. The X: autosome ratio regulate s XCI solely by promoting the spread of inactivation away from the Xic on chromosomes that express Xist. Methylation of the maternal Xist ge ne is retained in extraembryonic tissues, so that gynogenones and part henogenones cannot express Xist, do not undergo XCI in those tissues, and so have extraembryonic defects. This model should be relevant to u nderstanding how aberrant X chromosome regulation might occur and how this might contribute to distortion of the X-chromosome-transmission r atio, sex ratio distortion, and disease.