MERVL-driven Pcgf5 plays a critical role in the suppression of zygotic genome activation in preimplantation embryos
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE328704 | GEO | 2026/04/27
REPOSITORIES: GEO
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Project description:MERVL-driven Pcgf5 plays a critical role in the suppression of zygotic genome activation in preimplantation embryos
| PRJNA1456176 | ENA
Project description:Polycomb-group proteins are key regulators of the transcriptional programs that maintain stem cell identity and dictate lineage specification. Polycomb repressor complex 1 (PRC1) contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1) to regulate gene expression. PRC1 has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we find that Pcgf5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway. Inhibition of SMAD2/TGF-β signaling or rescue by overexpression of Pcgf5 can restore the capability of mESCs to differentiate towards a neural cell fate. PCGF5 works by stimulating RING1B-dependent H2AK119ub1 both in vitro and in vivo, leading to the suppression of TGF-β signaling genes. PCGF5 loss-of-function prevents the reduction of H2AK119ub1 and H3K27me3 around neural specific genes and keeps them repressed. Our results showed that PCGF5 might function as both a repressor for SMAD2/TGF-β signaling pathway and a facilitator for neural differentiation. Together, our findings reveal a critical context-specific function for PCGF5 in directing PRC1 to control cell fate.
2018-03-10 | GSE107377 | GEO
Project description:Polycomb-group proteins are key regulators of the transcriptional programs that maintain stem cell identity and dictate lineage specification. Polycomb repressor complex 1 (PRC1) contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1) to regulate gene expression. PRC1 has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we find that Pcgf5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway. Inhibition of SMAD2/TGF-β signaling or rescue by overexpression of Pcgf5 can restore the capability of mESCs to differentiate towards a neural cell fate. PCGF5 works by stimulating RING1B-dependent H2AK119ub1 both in vitro and in vivo, leading to the suppression of TGF-β signaling genes. PCGF5 loss-of-function prevents the reduction of H2AK119ub1 and H3K27me3 around neural specific genes and keeps them repressed. Our results showed that PCGF5 might function as both a repressor for SMAD2/TGF-β signaling pathway and a facilitator for neural differentiation. Together, our findings reveal a critical context-specific function for PCGF5 in directing PRC1 to control cell fate.
2018-03-10 | GSE95127 | GEO
Project description:We obtained H3K27me3 profiles in mouse morula stage embryos (72 h post-insemination (hpi)) which had been in vitro treated with siRNA targeting Pcgf5 from one-cell stage (3 hpi).
2024-11-07 | GSE280946 | GEO
Project description:Polycomb repressive complexes 1 and 2 (PRC1/2) maintain transcriptional silencing of developmental genes largely by catalyzing mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub1) and trimethylation of histone H3 at lysine 27 (H3K27me3), respectively. How Polycomb domains are reprogrammed during mammalian preimplantation development remains largely unclear. Here we show that, although H2AK119ub1 and H3K27me3 are highly colocalized in gametes, they undergo differential reprogramming dynamics following fertilization. H3K27me3 maintains thousands of maternally biased domains up to the blastocyst stage, whereas maternally biased H2AK119ub1 distribution in zygotes is largely equalized at the two-cell stage. Notably, while maternal PRC2 depletion has a limited effect on global H2AK119ub1 in early embryos, it disrupts allelic H2AK119ub1 at H3K27me3 imprinting loci including Xist. By contrast, acute H2AK119ub1 depletion in zygotes does not affect H3K27me3 imprinting maintenance, at least by the four-cell stage. Importantly, loss of H2AK119ub1, but not H3K27me3, causes premature activation of developmental genes during zygotic genome activation (ZGA) and subsequent embryonic arrest. Thus, our study reveals distinct dynamics and functions of H3K27me3 and H2AK119ub1 in mouse preimplantation embryos.
2021-03-15 | GSE158360 | GEO
Project description:Polycomb repressive complexes 1 and 2 (PRC1/2) maintain transcriptional silencing of developmental genes largely by catalyzing mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub1) and trimethylation of histone H3 at lysine 27 (H3K27me3), respectively. How Polycomb domains are reprogrammed during mammalian preimplantation development remains largely unclear. Here we show that, although H2AK119ub1 and H3K27me3 are highly colocalized in gametes, they undergo differential reprogramming dynamics following fertilization. H3K27me3 maintains thousands of maternally biased domains up to the blastocyst stage, whereas maternally biased H2AK119ub1 distribution in zygotes is largely equalized at the two-cell stage. Notably, while maternal PRC2 depletion has a limited effect on global H2AK119ub1 in early embryos, it disrupts allelic H2AK119ub1 at H3K27me3 imprinting loci including Xist. By contrast, acute H2AK119ub1 depletion in zygotes does not affect H3K27me3 imprinting maintenance, at least by the four-cell stage. Importantly, loss of H2AK119ub1, but not H3K27me3, causes premature activation of developmental genes during zygotic genome activation (ZGA) and subsequent embryonic arrest. Thus, our study reveals distinct dynamics and functions of H3K27me3 and H2AK119ub1 in mouse preimplantation embryos.
2021-03-15 | GSE153529 | GEO
Project description:Polycomb repressive complexes 1 and 2 (PRC1/2) maintain transcriptional silencing of developmental genes largely by catalyzing mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub1) and trimethylation of histone H3 at lysine 27 (H3K27me3), respectively. How Polycomb domains are reprogrammed during mammalian preimplantation development remains largely unclear. Here we show that, although H2AK119ub1 and H3K27me3 are highly colocalized in gametes, they undergo differential reprogramming dynamics following fertilization. H3K27me3 maintains thousands of maternally biased domains up to the blastocyst stage, whereas maternally biased H2AK119ub1 distribution in zygotes is largely equalized at the two-cell stage. Notably, while maternal PRC2 depletion has a limited effect on global H2AK119ub1 in early embryos, it disrupts allelic H2AK119ub1 at H3K27me3 imprinting loci including Xist. By contrast, acute H2AK119ub1 depletion in zygotes does not affect H3K27me3 imprinting maintenance, at least by the four-cell stage. Importantly, loss of H2AK119ub1, but not H3K27me3, causes premature activation of developmental genes during zygotic genome activation (ZGA) and subsequent embryonic arrest. Thus, our study reveals distinct dynamics and functions of H3K27me3 and H2AK119ub1 in mouse preimplantation embryos.
2021-03-15 | GSE153530 | GEO
Project description:We systematically analyzed transcriptome in individual human oocytes and preimplantation embryos with a new single-cell RNA seq method we recently developed. We sequenced individual single cells or embryos at seven consecutive stages (mature oocytes, zygotes, 2-cell, 4-cell, 8-cell embryos, morulae, and blastocysts) and single hESC using single-cell RNA seq.
2016-05-13 | E-GEOD-71318 | biostudies-arrayexpress
Project description:Facultative heterochromatin is formed by Polycomb repressive complex 2 (PRC2)-deposited H3K27 tri-methylation (H3K27me3) and PRC1-deposited H2AK119 mono-ubiquitylation (H2AK119ub1). How it is newly established after fertilization remains unclear. To delineate the establishment kinetics, here we profiled the temporal dynamics of H3K27 di-methylation (H3K27me2), which represents the de novo PRC2 catalysis, in mouse preimplantation embryos. H3K27me2 is newly deposited at CpG islands (CGIs), the paternal X-chromosome (Xp), and putative enhancers during the 8-cell-to-morula transition, all of which follow H2AK119ub1 deposition. We found that JARID2, a PRC2.2-specific accessory protein possessing an H2AK119ub1-binding ability, colocalizes with SUZ12 at CGIs and Xp in morula embryos. Upon JARID2 depletion, SUZ12 chromatin binding and H3K27me2 deposition were attenuated and H3K27 acetylation was increased at putative enhancers in morulae, and subsequently H3K27me3 failed to be deposited in blastocysts. These data reveal that facultative heterochromatin is established by PRC2.2-driven stepwise H3K27 methylation along pre-deposited H2AK119ub1 during early embryogenesis.
2024-09-05 | GSE264193 | GEO
Project description:Facultative heterochromatin is formed by Polycomb repressive complex 2 (PRC2)-deposited H3K27 tri-methylation (H3K27me3) and PRC1-deposited H2AK119 mono-ubiquitylation (H2AK119ub1). How it is newly established after fertilization remains unclear. To delineate the establishment kinetics, here we profiled the temporal dynamics of H3K27 di-methylation (H3K27me2), which represents the de novo PRC2 catalysis, in mouse preimplantation embryos. H3K27me2 is newly deposited at CpG islands (CGIs), the paternal X-chromosome (Xp), and putative enhancers during the 8-cell-to-morula transition, all of which follow H2AK119ub1 deposition. We found that JARID2, a PRC2.2-specific accessory protein possessing an H2AK119ub1-binding ability, colocalizes with SUZ12 at CGIs and Xp in morula embryos. Upon JARID2 depletion, SUZ12 chromatin binding and H3K27me2 deposition were attenuated and H3K27 acetylation was increased at putative enhancers in morulae, and subsequently H3K27me3 failed to be deposited in blastocysts. These data reveal that facultative heterochromatin is established by PRC2.2-driven stepwise H3K27 methylation along pre-deposited H2AK119ub1 during early embryogenesis.
2024-09-05 | GSE263441 | GEO