期刊
EPIGENETICS & CHROMATIN
卷 8, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s13072-015-0044-2
关键词
Imprinted X-inactivation; Trophoblast Stem cells; Epigenetic Reprogramming
资金
- Pasteur Institute
- French National Centre for Scientific Research (CNRS)
- French National Agency for Research (ANR)
- Epigenome Network of Excellence
- REVIVE Labex
- Louis D Foundation of the Institut de France
- Region Ile-de-France (DIM-Biotherapies)
- French National Institute for Scientific and Medical Research (INSERM)
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 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 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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