Maternal SMCHD1 controls both imprinted Xist expression and imprinted X chromosome inactivation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA773385 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16520900_1.fastq.gz | Fastqsanger.gz | |||
| SRR16520900_2.fastq.gz | Fastqsanger.gz | |||
| SRR16520901_1.fastq.gz | Fastqsanger.gz | |||
| SRR16520901_2.fastq.gz | Fastqsanger.gz | |||
| SRR16520902_1.fastq.gz | Fastqsanger.gz |
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Project description:Embryonic development is dependent on the maternal supply of proteins through the oocyte, including factors setting up the adequate epigenetic patterning of the zygotic genome. We previously reported that one such factor is the epigenetic repressor SMCHD1, whose maternal supply controls autosomal imprinted expression in mouse preimplantation embryos and mid-gestation placenta. In mouse preimplantation embryos, X chromosome inactivation is also an imprinted process. Combining genomics and imaging, we show that maternal SMCHD1 is required not only for the imprinted expression of Xist in preimplantation embryos, but also for the efficient silencing of the inactive X in both the preimplantation embryo and mid-gestation placenta. These results expand the role of SMCHD1 in enforcing the silencing of Polycomb targets. The inability of zygotic SMCHD1 to fully restore imprinted X inactivation further points to maternal SMCHD1's role in setting up the appropriate chromatin environment during preimplantation development, a critical window of epigenetic remodelling.
2021-10-24 | GSE186315 | GEO
Project description:Embryonic development is dependent on the maternal supply of proteins through the oocyte, including factors setting up the adequate epigenetic patterning of the zygotic genome. We previously reported that one such factor is the epigenetic repressor SMCHD1, whose maternal supply controls autosomal imprinted expression in mouse preimplantation embryos and mid-gestation placenta. In mouse preimplantation embryos, X chromosome inactivation is also an imprinted process. Combining genomics and imaging, we show that maternal SMCHD1 is required not only for the imprinted expression of Xist in preimplantation embryos, but also for the efficient silencing of the inactive X in both the preimplantation embryo and mid-gestation placenta. These results expand the role of SMCHD1 in enforcing the silencing of Polycomb targets. The inability of zygotic SMCHD1 to fully restore imprinted X inactivation further points to maternal SMCHD1's role in setting up the appropriate chromatin environment during preimplantation development, a critical window of epigenetic remodelling.
| S-EPMC9290310 | biostudies-literature
Project description:To investigate the effect of Smchd1 ablation on de novo X chromosome inactivation (XCI), we derived clonal neural progenitor cells (NPCs) from Smchd1+/+ (wild-type, WT) and Smchd1-/- mouse embryonic stem cells (ES cells; ESC). We generated allele-specific RNA-seq datasets from WT and Smchd1-/- NPCs to examine the effect of Smchd1 ablation on gene silencing. In addition, we produced allele-specific ChIP-seq profiles of H3K4me3, H3K27me3, CTCF, and RAD21 and Xist CHART-seq profiles in WT and Smchd1-/- NPCs to investigate the role of SMCHD1 on the distribution of euchromatin, facultative heterochromatin, architectural proteins, and Xist RNA on the inactive X chromosome (Xi). To determine the localization of SMCHD1 on the Xi, we employed allele-specific DamID-seq to map SMCHD1-binding regions in female mouse embryonic fibroblasts. Furthermore, we performed in situ Hi-C on WT NPCs, Smchd1-/- NPCs, and female ES cells undergoing XCI, in order to explore the role of SMCHD1 in regulating the higher-order structure of the Xi.
2018-06-07 | GSE99991 | GEO
Project description:In Mammals, the difference in sex-chromosome constitution between males (XY) and females (XX) has led to the evolution of dosage compensation strategies, including silencing of an entire X chromosome in females. In mice, X chromosome inactivation (XCI) first occurs in the pre-implantation embryo. Here the non-coding Xist RNA is expressed only from the paternal allele and the paternal X (Xp) becomes inactivated. The Xp is reactivated in the inner cell mass and this is followed by random XCI in the embryo proper, while in extra-embryonic tissues the Xp remains inactive. Although random XCI initiation is thought to be fully Xist-dependent in the mouse, initiation of imprinted XCI was reported to be Xist-independent. Furthermore, the chromosome-wide dynamics of XCI in early embryos of reciprocal inter-specific crosses, which better reflect a natural situation, have never been investigated. Here we report that the expression dynamics of X-linked genes depends both on strain and parent of origin, as well as on X chromosome location, using single-cell RNA-sequencing (scRNAseq) of early mouse embryos. We also demonstrate that initiation of imprinted XCI absolutely requires Xist and that its absence leads to genome-wide transcriptional misregulation in the early blastocyst, with massive over-expression of specific genes such as Rhox5 and failure to activate the extra-embryonic pathway essential for early post-implantation development. This study provides important insights into the transcriptional and allelic dynamics of the X chromosome and the first evidence of dosage compensation failure as early as the blastocyst stage.
2016-12-05 | GSE80810 | GEO
Project description:Imprinted X-inactivation is a paradigm of transgenerational epigenetic inheritance in mammals and silences genes exclusively on the paternally-inherited X-chromosome. Here, we test the hypothesis that oocyte-derived maternal Polycomb repressive complex 2 (PRC2) protein EED orchestrates the selective inactivation of the paternal-X in mouse embryos. In maternal Eed null (Eedm-/-) but not zygotic Eed null female and male embryos, the maternal X-chromosome ectopically induced Xist lncRNA, which silences X-linked genes. Subsequently, Xist was silenced from one of the two X-chromosomes in females and from the sole maternal-X in males. As a result, later-stage female Eedm-/- embryos displayed random X-inactivation. The kinetics of Xist RNA induction in Eedm-/- embryos resemble that of early human embryos, which lack oocyte-derived PRC2 and only undergo random X-inactivation. Thus, expression of PRC2 genes in the oocyte and transmission of the gene products to the embryo may dictate the occurrence of imprinted X-inactivation in mammals.
2019-05-02 | GSE123173 | GEO
Project description:Xist-mediated Chromosome Inactivation
| PRJNA489702 | ENA
Project description:The role of Xist-mediated Polycomb recruitment in the initiation of X-chromosome inactivation
2019-08-29 | PXD014287 | Pride
Project description:The Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation (XCI), the process by which mammals compensate for unequal numbers of sex chromosomes. During XCI, Xist coats the future inactive X (Xi) and recruits Polycomb Repressive Complex 2 (PRC2) to the X-inactivation center (Xic). Currently unclear is how Xist spreads silencing on a 150 Mb scale. Here we generate high-resolution maps of Xist binding across a developmental time course using CHART-seq. In female cells undergoing XCI de novo, Xist follows a two-step mechanism in which it initially targets gene-rich islands before spreading to intervening gene-poor domains. Xist is depleted from genes that escape XCI but frequently concentrates near escapee boundaries. Xist binding was linearly proportional to PRC2 density and H3 lysine 27 trimethylation (H3K27me3), suggesting co-migration of Xist and PRC2. Interestingly, when the Xi is acutely stripped of Xist in post-XCI cells, Xist recovers quickly within both gene-rich and -poor domains on a time scale of hours instead of days, suggesting a previously primed Xi chromatin state. We conclude that Xist spreading takes on distinct stage-specific forms: During initial establishment, Xist follows a two-step mechanism, but during maintenance, Xist spreads rapidly to both gene-rich and -poor regions. Capture hybridization analysis of RNA targets (CHART) and input samples of (differentiating) mouse embryonic stem (ES) cells and immortalized mouse embryonic fibroblasts (MEF) using paired-end 75 nt reads on Illumina HiSeq2500, with 2 replicates per sample (# of samples). RNA-seq of the same cell lines with 50 nt reads on Illumina HiSeq2000, with 2 replicates per sample (2 samples, 4 datasets total). CHIP-seq: Data from GSE36905 was aligned and processed as CHART-seq samples. Resulting coverage tracks (EZH2/K27me3) are linked directly to GSE48649 (bedGraphs linked below).
2013-11-04 | E-GEOD-48649 | biostudies-arrayexpress
Project description:Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X chromosome inactivation (XCI) in female mammals. However, the mechanism underlying the Xist imprinting is unclear. Here we show that the Xist gene is coated with H3K27me3 in mouse oocytes, which persists through preimplantation development. Ectopic removal of H3K27me3 induces maternal Xist expression and maternal XCI, indicating that maternal H3K27me3 is the imprinting mark of Xist.
2017-11-09 | GSE103714 | GEO
Project description:The Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation (XCI), the process by which mammals compensate for unequal numbers of sex chromosomes. During XCI, Xist coats the future inactive X (Xi) and recruits Polycomb Repressive Complex 2 (PRC2) to the X-inactivation center (Xic). Currently unclear is how Xist spreads silencing on a 150 Mb scale. Here we generate high-resolution maps of Xist binding across a developmental time course using CHART-seq. In female cells undergoing XCI de novo, Xist follows a two-step mechanism in which it initially targets gene-rich islands before spreading to intervening gene-poor domains. Xist is depleted from genes that escape XCI but frequently concentrates near escapee boundaries. Xist binding was linearly proportional to PRC2 density and H3 lysine 27 trimethylation (H3K27me3), suggesting co-migration of Xist and PRC2. Interestingly, when the Xi is acutely stripped of Xist in post-XCI cells, Xist recovers quickly within both gene-rich and -poor domains on a time scale of hours instead of days, suggesting a previously primed Xi chromatin state. We conclude that Xist spreading takes on distinct stage-specific forms: During initial establishment, Xist follows a two-step mechanism, but during maintenance, Xist spreads rapidly to both gene-rich and -poor regions.
2013-11-04 | GSE48649 | GEO