Initiation of X chromosome inactivation in rabbit and human embryos
Résumé
X-chromosome inactivation (XCI) in female mammals enables dosage compensation for X- linked gene products between the sexes. The developmental regulation of this process has been extensively investigated in mice, where the X chromosome of paternal origin is silenced during early embryogenesis due to imprinted expression of the regulatory RNA, Xist (X-inactive-specific-transcript). Paternal XCI is reversed in the inner cell mass (ICM) of the blastocyst and random XCI subsequently occurs in epiblast cells. At the opposite, paternal XCI is maintained in extraembryonic tissues. The aim of this study was to analyze initiation of X inactivation in eutherian non murine species. Therefore we choose rabbit because it is phylogenetically close to mouse, and human. We performed RNA/ DNA FISH experiments in rabbit and human early embryos to analyze at the single cell level the expression of Xist, Hprt/ATRX : two genes submitted to X-inactivation in somatic rabbit and human cells, and Jarid1c which escapes X-inactivation. Our results show that eutherian mammals have very different strategies to initiate XCI. In rabbits and humans, XCI begins later than in mice and the Xist homologue is not subject to imprinting. In fact Xist is expressed in both male and female embryos and is up-regulated on both chromosomes in a high proportion of rabbit and human female embryo cells, even in the ICM contrarily to mouse embryos where only females express Xist and where no biallelic expression of Xist occurs in normal embryos. In rabbit this triggers XCI on both X chromosomes in some cells. In humans, XCI has not initiated even by the blastocyst stage. The choice of which X chromosome will finally become inactive thus occurs downstream of Xist upregulation in both rabbits and humans, unlike in mice. These results demonstrate the remarkable diversity in XCI regulation and highlight differences between mammals in their requirement for dosage compensation during early embryogenesis.