Epigenetic regulation of reactivation of the silenced X-chromosome during mouse germline development
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ABSTRACT:
PROVIDER: PRJEB79413 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR13604500_1.fastq.gz | Fastqsanger.gz | |||
| ERR13604500_2.fastq.gz | Fastqsanger.gz | |||
| ERR13604501_1.fastq.gz | Fastqsanger.gz | |||
| ERR13604501_2.fastq.gz | Fastqsanger.gz | |||
| ERR13604502_1.fastq.gz | Fastqsanger.gz |
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Project description:Reactivation of the silenced X-chromosome during mouse germline development
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Project description:X chromosome reactivation (XCR) occurs over a prolonged period during genome-wide reprogramming in female germ cells, initiating soon after primordial germ cell specification. The kinetics of XCRs remain poorly understood, as previous studies of XCR were based on a few genes. For a global appraisal of the regulation of XCR dynamics, we performed matched CUT&RUN for H3K27me3 and H2AK119ub1 on F1 female (XX(Xist∆)) germ cells at E13.5 and E16.5 stages during embryonic development.
2024-12-11 | E-MTAB-13576 | biostudies-arrayexpress
Project description:X chromosome reactivation (XCR) occurs over a prolonged period during genome-wide reprogramming in female germ cells, initiating soon after primordial germ cell specification. The kinetics of XCRs remain poorly understood, as previous studies of XCR were based on a few genes. For a global appraisal of XCR dynamics, we performed single-cell RNA-seq on F1 female (XX(Xist∆)) and male (XY) germ cells from E9.5 to E16.5 stages in development. Through the incorporation of interspecific crosses between C57B6J (B6) and Castaneus (CAST) parental mouse strains, containing a high number of informative single-nucleotide variants, we are able to distinguish gene expression from parental chromosomes in F1 embryos computationally.
2024-12-11 | E-MTAB-13535 | biostudies-arrayexpress
Project description: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 on in vivo developing mouse PGC, we provide unprecedented detailed maps of gene reactivation. We demonstrate that PGC still carry a fully silent X chromosome at 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.
2025-01-06 | GSE243941 | GEO
Project description:Rett Syndrome is a neurodevelopmental disorder in girls that is caused by heterozygous inactivation of the chromatin remodeler gene MECP2. Rett Syndrome may therefore be treated by reactivation of the wild type copy of MECP2 from the inactive X chromosome. Most studies that model Mecp2 reactivation have used mouse fibroblasts rather than neural cells, which would be critical for phenotypic reversal, and rely on fluorescent reporters that lack adequate sensitivity. Here, we present a mouse model system for monitoring Mecp2 reactivation that is more sensitive and versatile than any bioluminescent and fluorescent system currently available. The model consists of neural stem cells derived from female mice with a dual reporter system where MECP2 is fused to NanoLuciferase and TdTomato on the inactive X chromosome. We show by bioluminescence and fluorescence that Mecp2 is synergistically reactivated by 5-Aza treatment and Xist knockdown. As expected, other genes on the inactive X chromosome are also reactivated, the majority of which overlaps with genes reactivated early during reprogramming of mouse embryonic fibroblasts to iPSCs. Genetic and epigenetic features such as CpG density, SINE elements, distance to escapees and CTCF binding are consistent indicators of reactivation, whereas different higher order chromatin areas are either particularly prone or resistant to reactivation. Our MeCP2 reactivation monitoring system thereby suggests that genetic and epigenetic features on the inactive X chromosome affect reactivation of its genes, irrespective of cell type or procedure of reactivation.
2022-01-24 | GSE166146 | GEO
Project description:Rett Syndrome is a neurodevelopmental disorder in girls that is caused by heterozygous inactivation of the chromatin remodeler gene MECP2. Rett Syndrome may therefore be treated by reactivation of the wild type copy of MECP2 from the inactive X chromosome. Most studies that model Mecp2 reactivation have used mouse fibroblasts rather than neural cells, which would be critical for phenotypic reversal, and rely on fluorescent reporters that lack adequate sensitivity. Here, we present a mouse model system for monitoring Mecp2 reactivation that is more sensitive and versatile than any bioluminescent and fluorescent system currently available. The model consists of neural stem cells derived from female mice with a dual reporter system where MECP2 is fused to NanoLuciferase and TdTomato on the inactive X chromosome. We show by bioluminescence and fluorescence that Mecp2 is synergistically reactivated by 5-Aza treatment and Xist knockdown. As expected, other genes on the inactive X chromosome are also reactivated, the majority of which overlaps with genes reactivated early during reprogramming of mouse embryonic fibroblasts to iPSCs. Genetic and epigenetic features such as CpG density, SINE elements, distance to escapees and CTCF binding are consistent indicators of reactivation, whereas different higher order chromatin areas are either particularly prone or resistant to reactivation. Our MeCP2 reactivation monitoring system thereby suggests that genetic and epigenetic features on the inactive X chromosome affect reactivation of its genes, irrespective of cell type or procedure of reactivation.
2022-01-24 | GSE166145 | GEO
Project description: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 on in vivo developing mouse PGC, we provide unprecedented detailed maps of gene reactivation. We demonstrate that PGC still carry a fully silent X chromosome at 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.
2025-01-06 | GSE243942 | GEO
Project description:Epigenetic modifications that arise during plant and animal development, such as DNA and histone modification, are mostly reset during gamete formation, but some are inherited from the germline including those marking imprinted genes. Small RNAs guide these epigenetic modifications, and some are also inherited by the next generation. In C. elegans, inherited small RNA precursors have poly (UG) tails, but how inherited small RNAs are distinguished in other animals and plants is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop novel assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs and their precursors. We also detect substantial enrichment in germline small RNAs, namely epigenetically activated siRNAs (easiRNAs) in Arabidopsis pollen, and piwi-interacting piRNAs in mouse testis. In pollen, pseudouridylated easiRNAs are localized to sperm cells, and we found that PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for transport of easiRNAs into sperm cells from the vegetative nucleus. We further show that Exportin-t is required for the triploid block: chromosome dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.
2024-04-29 | PXD042662 | Pride
Project description:In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes, however the molecular mechanisms of this specificity remain unclear. Here we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in vivo, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long term epigenetic silencing during mammalian development.
2021-04-22 | PXD023974 | Pride
Project description:Reprogramming to iPSCs resets the epigenome of somatic cells including the reversal of X chromosome-inactivation. We sought to gain insight into the steps underlying the reprogramming process by examining the means by which reprogramming leads to X chromosome-reactivation (XCR). Analyzing single cells in situ, we found that hallmarks of the inactive X (Xi) change sequentially, providing a direct readout of reprogramming progression. Several epigenetic changes on the Xi occur in the inverse order of developmental X-inactivation, while others are uncoupled from this sequence. Among the latter, DNA methylation has an extraordinary long persistence on the Xi during reprogramming, and, like Xist expression, is erased only after pluripotency genes are activated. Mechanistically, XCR requires both DNA demethylation and Xist silencing, ensuring that only cells undergoing faithful reprogramming initiate XCR. Our study defines the epigenetic state of multiple sequential reprogramming intermediates and establishes a paradigm for studying cell fate transitions during reprogramming. RRBS profiles were generated from female and male ES cells, female iPS cells, SSEA1+ and SSEA1- reprogramming intermediates, and male and female MEFs, for a total of 18 samples.
2014-12-18 | E-GEOD-58109 | biostudies-arrayexpress