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A rapid passage through a two-active-X-chromosome state accompanies the switch of imprinted X-inactivation patterns in mouse trophoblast stem cells

Abstract : BACKGROUND: In female mice, while the presence of two-active X-chromosomes characterises pluripotency, it is not tolerated in most other cellular contexts. In particular, in the trophoblastic lineage, impairment of paternal X (X(P)) inactivation results in placental defects. RESULTS: Here, we show that Trophoblast Stem (TS) cells can undergo a complete reversal of imprinted X-inactivation without detectable change in cell-type identity. This reversal occurs through a reactivation of the X(P) leading to TS clones showing two active Xs. Intriguingly, within such clones, all the cells rapidly and homogeneously either re-inactivate the X(P) or inactivate, de novo, the X(M). CONCLUSION: This secondary non-random inactivation suggests that the two-active-X states in TS and in pluripotent contexts are epigenetically distinct. These observations also reveal a pronounced plasticity of the TS epigenome allowing TS cells to dramatically and accurately reprogram gene expression profiles. This plasticity may serve as a back-up system when X-linked mono-allelic gene expression is perturbed.
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Julie Prudhomme, Agnès Dubois, Pablo Navarro Gil, Danielle Arnaud, Philip Avner, et al.. A rapid passage through a two-active-X-chromosome state accompanies the switch of imprinted X-inactivation patterns in mouse trophoblast stem cells. Epigenetics & Chromatin, BioMed Central, 2015, 8, pp.52. ⟨10.1186/s13072-015-0044-2⟩. ⟨pasteur-02024892⟩

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