Spatio-temporal X-linked gene reactivation and site-specific retention of epigenetic silencing in the in vivo germline.

Roidor, C.; Syx, L.; Beyne, E.; Zielinski, D.; Teissandier, A.; Lee, C.; Walter, M.; Servant, N.; Chebli, K.; Bourc'his, D.; Surani, M. A.; Borensztein, M.

doi:10.1101/2023.04.25.532252

bioRxiv · 10.1101/2023.04.25.532252

Spatio-temporal X-linked gene reactivation and site-specific retention of epigenetic silencing in the in vivo germline.

Roidor, C.·Syx, L.·Beyne, E.·Zielinski, D.·Teissandier, A.·Lee, C.·Walter, M.·Servant, N.·Chebli, K.·Bourc'his, D.·Surani, M. A.·Borensztein, M.

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Abstract

Random X-chromosome inactivation (XCI) is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long non-coding RNA Xist, occurs in the epiblast and is stably maintained to ensure proper dosage compensation of X-linked genes during life. However, this silencing is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling in developing in vivo PGC, we provide unprecedented detailed maps of gene reactivation. We demonstrated that PGC still carry a fully silent X chromosome on embryonic day (E) 9.5, despite the loss of Xist expression. X-linked genes are then gradually reactivated outside the Xist first-bound regions. At E12.5, a significant part of the inactive X chromosome (Xi) still resists reactivation, carrying an epigenetic memory of its silencing. Late-reactivated genes are enriched in repressive chromatin marks, including DNA methylation and H3K27me3 marks. Our results define the timing of reactivation of the silent X chromosome a key event in female PGC reprogramming with direct implications for reproduction.

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Roidor, C., Syx, L., Beyne, E., Zielinski, D., Teissandier, A., Lee, C., Walter, M., Servant, N., Chebli, K., Bourc'his, D., Surani, M. A., Borensztein, M.. 2023-04-26. Spatio-temporal X-linked gene reactivation and site-specific retention of epigenetic silencing in the in vivo germline.. https://doi.org/10.1101/2023.04.25.532252

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