Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01415-5
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Funding
- Region Ile-de-France (DIM STEMPOLE)
- Fondation Recherche Medicale [FRM SPE20150331826]
- Marie Sklodowska-Curie Individual Fellowship (H-MSCA-IF) [706144]
- CELLECTCHIP [ANR-14-CE10-0013]
- Paris Alliance of Cancer Research Institutes (PACRI-ANR)
- ERC Advanced Investigator award (ERC-AdG) [250367]
- EU FP7 grants SYBOSS (EU seventh Framework G.A.) [242129]
- MODHEP (EU seventh Framework G.A.) [259743]
- La Ligue
- France Genomique National infrastructure [ANR-10-INBS-09]
- MEXT
- JST-ERATO
- JSPS KAKENHI Grant [JP25291076]
- DFG [SPP1356]
- MRC [U105178808]
- Fondation de France
- Labex DEEP, IDEX Idex PSL [ANR-11-LBX-0044, ANR-10-IDEX-0001-02 PSL]
- ABS4NGS [ANR-11-BINF0001]
- Marie Curie Actions (MSCA) [706144] Funding Source: Marie Curie Actions (MSCA)
- Medical Research Council [MC_U105178808] Funding Source: researchfish
- MRC [MC_U105178808] Funding Source: UKRI
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X-chromosome inactivation is established during early development. In mice, transcriptional repression of the paternal X-chromosome (Xp) and enrichment in epigenetic marks such as H3K27me3 is achieved by the early blastocyst stage. X-chromosome inactivation is then reversed in the inner cell mass. The mechanisms underlying Xp reactivation remain enigmatic. Using in vivo single-cell approaches (allele-specific RNAseq, nascent RNA-fluorescent in situ hybridization and immunofluorescence), we show here that different genes are reactivated at different stages, with more slowly reactivated genes tending to be enriched in H3meK27. We further show that in UTX H3K27 histone demethylase mutant embryos, these genes are even more slowly reactivated, suggesting that these genes carry an epigenetic memory that may be actively lost. On the other hand, expression of rapidly reactivated genes may be driven by transcription factors. Thus, some X-linked genes have minimal epigenetic memory in the inner cell mass, whereas others may require active erasure of chromatin marks.
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