International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

A12 Effects of X Chromosome Number and Parental Origin on X-Linked Gene Expression in Preimplantation Mouse Embryos

Keith E. Latham1,2 , Bela Patel1, F. Dale, M. Bautista1, and Susan M. Hawes1. 1The Fels Institute for Cancer Research and Molecular Biology; 2Department of Biochemistry, Temple University School of Medicine

Diploid androgenetic mouse embryos, possessing two sets of paternally inherited chromosomes, and control fertilized embryos were used to examine the relative effects of X chromosome number and parental chromosome origin on androgenone viability and X-linked gene expression. A significant difference in viability was observed between XX and XY androgenones in some experiments, but this difference was not uniformly observed. Significant effects of both X chromosome number and parental origin on X-linked gene expression were observed. Male and female control embryos expressed the Xist RNA initially. This was followed by a preferential reduction in Xist RNA abundance in male embryos, coincident with an apparent onset of dosage compensation in late blastocyst stage embryos. This indicates that during normal embryogenesis dosage compensation for the X chromosome requires the downregulation of Xist RNA expression in male embryos, possibly in conjunction with a shift in promoter usage to produce more stable Xist transcripts in female embryos. Like their normal counterparts, XX androgenetic blastocysts initially expressed more Xist RNA than XY androgenetic blastocysts. This result indicates that X chromosome counting mechanisms operate in the preimplantation embryo and are insensitive to genomic imprinting. The XX:XY Xist expression ratio decreased in androgenones with continued development, indicating that androgenones are either unable to maintain Xist gene transcription or unable to shift promoter usage to the production of stable Xist RNA transcripts. Androgenones also exhibited severe repression of the Pgk1 gene, with repression initially greater in XX androgenones than in XY androgenones. The initial repression of the Pgk1 was lost as the Xist RNA declined in abundance. Thus, X chromosome dosage compensation mechanisms appear to function initially in androgenones, but their effects are unstable due to a failure to maintain Xist RNA expression. These results indicate that dosage compensation in preimplantation embryos requires Xist RNA stabilization, as has been demonstrated for embryonic lineages at later stages of development. Our results also indicate that early dosage compensation in preimplantation embryos may normally be reversible through a developmentally regulated change in Xist RNA synthesis or stability, thus providing flexibility to meet different developmental requirements of the embryonic and extraembryonic lineages.

 


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