A rapid passage through a two-active-X-chromosome state accompanies the switch of imprinted X-inactivation patterns in mouse trophoblast stem cells. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Prudhomme, Julie; Dubois, Agnès; Navarro, Pablo; Arnaud, Danielle; Avner, Philip; Morey, Céline
• Is Part Of: Epigenetics & chromatin. Volume 8:Issue 1(2015)
• Page Start: 1
• Page End: 15
• Publication Date: 2015-12
• Subjects: Imprinted X-inactivation -- Trophoblast Stem cells -- Epigenetic Reprogramming; Epigenesis -- Periodicals; Chromatin -- Periodicals; 572.8
• DOI: 10.1186/s13072-015-0044-2
• Languages: English
• ISSNs: 1756-8935

Abstract

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 (XP ) 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 XP leading to TS clones showing two active Xs. Intriguingly, within such clones, all the cells rapidly and homogeneously either re-inactivate the XP or inactivate, de novo, the XM . 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.