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03.11.17 X-chromosome reactivation in the inner cell mass happens at different stages for different genes

last modified Nov 13, 2017 09:47 AM
Borensztein et al. show in this Nature Communications paper that different genes on the paternal X-chromosome may be reactivated by transcription factors or active erasure of chromatin marks
03.11.17 X-chromosome reactivation in the inner cell mass happens at different stages for different genes

Fig. 2a (excerpt): Inner cell mass showing H3K27 tri-methylation (grey scale), Xist RNA (green) and primary transcription from an X-linked gene (red).

Contribution of epigenetic landscapes and transcription factors to X-chromosome reactivation in the inner cell mass

Borensztein M et al. (2017) Nat Commun. 8(1):1297. DOI: 10.1038/s41467-017-01415-5.



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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