X-chromosome inactivation (XCI) enables dosage compensation between XX females and XY males, and its absence causes lethality, owing to defects in extra-embryonic tissues. However, it has also been shown that some genes are able to escape XCI in these tissues. Here, Catherine Corbel, Edith Heard and colleagues reconcile these findings and show that the inactive X (Xi) in one particular extra-embryonic cell type – trophoblast giant cells (TGCs) – has an unusual chromatin status (). Using RNA FISH on sections of postimplantation mouse embryos, they show that XCI is maintained in embryonic lineages, whereas TGCs show a high level of escape from XCI. Partial re-expression of most X-linked genes analysed, with the exception of the G6pd housekeeping gene, was observed in TGCs. In addition, the Xi in TGCs possesses an unusual organization and chromatin status, exhibiting both active and inactive chromatin marks. The authors propose that this apparent ‘bivalence’ of the Xi might account for its instability in TGCs and suggest that additional mechanisms maintain silencing at key loci.
