Sex-specific chromatin remodelling safeguards transcription in germ cells

Huang, Tien-Chi; Wang, Yi Fang; Vazquez-Ferrer, Eric; Theofel, Ina; Requena, Cristina E.; Hanna, Courtney W.; Kelsey, Gavin; Hájková, Petra

doi:10.1038/s41586-021-04208-5

Cited by 35 publications

(33 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In PGCs, PRC1 directly regulates expression of germline genes to coordinate the timing of sexual differentiation 12 . In female PGCs, MPI is initiated through activation of germline genes by DNA demethylation [13][14][15] and release from Polycomb-mediated silencing [16][17][18][19] . In the female germline, various histone modifications and DNA methylation are established during oocyte growth 20,21 .…”

mentioning

confidence: 99%

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

Yeh

Munakata

et al. 2022

Nat Commun

View full text Add to dashboard Cite

The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.

show abstract

mentioning

confidence: 99%

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

Yeh

Munakata

et al. 2022

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Here, we show that EED (a binding partner of PRC1 proteins) is also necessary to repress Stra8 in XX PGCs at E11.5. Intriguingly, a conditional deletion of Eed (this study) and Ezh2 (Huang et al, 2021) in PGCs has no effect on the global levels of H2AK119ub1 in PGC nuclei. Similarly, loss of Rnf2 does not affect the global levels pf H3K27me3 (Yokobayashi et al, 2013).…”

Section: Discussionmentioning

confidence: 53%

EED is required for mouse primordial germ cell differentiation in the embryonic gonad

et al. 2022

View full text Add to dashboard Cite

“…Strikingly, we saw significant levels of H3K27me3 at IAPEz elements in NPCs, which was completely absent in ESCs (Figure 3c, Supplementary Figure 3b). While H3K27me3 has been documented to safeguard IAP silencing in germ cells (Huang et al, 2021) and upon induced loss of DNA methylation in ESCs (Walter et al, 2016), an epigenetic switch from H3K9me3 to H3K27me3 at IAPs has not been reported during NPC differentiation and further highlights IAPEzs as dynamically regulated sequences in neural development. We next looked at RNA expression of IAPEz elements in both cell types, as a proxy for the potential emergence of co-option events.…”

Section: Resultsmentioning

confidence: 99%

Co-option of endogenous retroviruses through genetic escape from TRIM28 repression

Enriquez-Gasca

Gould

Tunbak

et al. 2022

Preprint

View full text Add to dashboard Cite

Endogenous retroviruses (ERVs) have rewired host gene networks through co-option of their enhancers. To explore which ERVs get co-opted and why, we tracked the epigenetic fate of murine IAPEz elements using an in vitro model of embryonic stem cell (ESC) to neural progenitor cell (NPC) differentiation. TRIM28-repression depended on a 190bp sequence, previously shown to confer IAPEzs with retrotransposition activity. A subset of IAPEzs (~15%) exhibit genetic divergence from this sequence, which we term escapees. While repressed IAPEzs succumb to a previously undocumented epigenetic handover from H3K9me3 in ESCs to H3K27me3 in NPCs, escapee IAPEzs evade repression, resulting in their transcriptional derepression in NPCs. Escapee IAPEzs enhance expression of nearby neural genes and contribute to gene expression differences between mouse strains, which we discern by employing IAPEz insertion polymorphisms. In sum, co-opted ERVs stem from genetic escapees that have lost vital sequences required for both TRIM28 restriction and autonomous retrotransposition.

show abstract

Sex-specific chromatin remodelling safeguards transcription in germ cells

Cited by 35 publications

References 64 publications

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

EED is required for mouse primordial germ cell differentiation in the embryonic gonad

Co-option of endogenous retroviruses through genetic escape from TRIM28 repression

Contact Info

Product

Resources

About