Incomplete X-inactivation initiated by a hypomorphic Xist allele in the mouse
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE27373 | GEO | 2011/03/30
SECONDARY ACCESSION(S): PRJNA137277
REPOSITORIES: GEO
Similar Datasets
Project description:Mammals have evolved a mechanism to compensate for the difference in the number of X chromosome genes between XX females and XY males by inactivating one of the two X chromosomes in females. This X chromosome inactivation phenomenon is triggered by Xist gene, which is essential for X-inactivation to occur in cis. We demonstrate that an Xist mutant, XistIVS, is unique in that it retains a partial function to silence the X chromosome, which would provide an opportunity to dissect the molecular mechanism of Xist RNA-mediated chromosome silencing. To study the effect of XistIVS mutation on silencing of X-linked genes, global expression levels of X-linked genes were measured in mutant and control cells. We used female trophoblast stem (TS) cells carrying XistIVS mutation and gene expression was assayed using microarray containing 572 probes corresponding most of the X-linked genes. Then the result was compared with that obtained from wild-type control cells.
2011-03-30 | E-GEOD-27373 | biostudies-arrayexpress
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:Abdominal aortic aneurysms (AAAs) are a prevalent and deadly human pathology with strong sexual dimorphism. Research demonstrates that sex hormones influence, but do not fully explain, male versus female AAA pathology. In addition to sex hormones, the X and Y sex chromosomes, and their unique complements of genes, may contribute to sexually dimorphic AAA pathology. Here, for the first time, we defined the effect of female (XX) versus male (XY) chromosome complement on AAA formation and rupture in phenotypically female mice using an established murine model. Abdominal aortas from female mice bearing the XY chromosome selectively expressed Y chromosome genes, while genes known to escape X-inactivation were higher in XX females. The majority of gene differences in XY females fell within inflammatory pathways. When XY females were infused with AngII, AAA incidences doubled and aneurysms ruptured. AAAs from XY females exhibited significant inflammation. Moreover, infusion of AngII to XY females augmented aortic activity of matrix metalloproteinases. Finally, testosterone exposure applied chronically, or as a single bolus at postnatal day 1, markedly worsened AAA outcomes in XY compared to XX females. These results demonstrate that an XY sex chromosome complement profoundly influences aortic gene expression profiles and promotes AAA severity.
2016-11-07 | GSE81580 | GEO
Project description:Identification of cell type-specific XIST co-factors during maintenance of X chromosome inactivation by XIST CHIRP-MS
2021-03-08 | PXD023516 | Pride
Project description:Xist-mediated Chromosome Inactivation
| PRJNA489702 | ENA
Project description:X-chromosome inactivation (XCI) is a global silencing mechanism by which XX and XY mammals equalize X-linked gene dosages. XCI begins with an establishment phase during which Xist RNA spreads and induces de novo heterochromatinization across a female X chromosome, and is followed by a maintenance phase when multiple epigenetic pathways lock down the inactive X (Xi) state. Involvement of Polycomb repressive complexes 1 and 2 in XCI has been intensively studied, but with conflicting conclusions regarding their recruitment and role in Xi silencing. Here we reveal that establishment of XCI has two phases and reconcile the roles that Xist Repeats A and B play in gene silencing and Polycomb recruitment. Repeat A initiates both processes, whereas Repeat B bolsters or stabilizes them thereafter. Once established, XCI no longer requires Repeat A during maintenance. These findings integrate disparate studies and present a unified view of Xist?s role in Polycomb-mediated silencing.
2020-06-15 | GSE135389 | GEO
Project description:Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long noncoding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex, comprised of numerous autoantigenic components, is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multiorgan pathology in pristane-induced model of lupus than wild-type males. Xist expression in males reprogrammed T and B cell population and chromatin states to more resemble wild type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity.
2024-02-01 | GSE249829 | GEO
Project description:Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long noncoding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex, comprised of numerous autoantigenic components, is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multiorgan pathology in pristane-induced model of lupus than wild-type males. Xist expression in males reprogrammed T and B cell population and chromatin states to more resemble wild type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity.
2024-02-01 | GSE249828 | GEO
Project description:Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long noncoding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex, comprised of numerous autoantigenic components, is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multiorgan pathology in pristane-induced model of lupus than wild-type males. Xist expression in males reprogrammed T and B cell population and chromatin states to more resemble wild type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity.
2024-02-01 | GSE249827 | GEO
Project description:X chromosome inactivation (XCI) in mammals is mediated by Xist RNA which functions in cis to silence genes on a single X chromosome in XX female cells, thereby equalising levels of X-linked gene expression relative to XY males. XCI progresses over a period of several days, with some X-linked genes silencing faster than others. Chromosomal location of a gene is an important determinant of silencing rate, but uncharacterised gene-intrinsic features also mediate resistance or susceptibility to silencing. In this study, we examine mouse embryonic stem cell lines with an inducible Xist allele (iXist-ChrX mESCs) and integrate allele-specific data of gene silencing and decreasing inactive X (Xi) chromatin accessibility over time-courses of Xist induction with cellular differentiation. Our analysis reveals that motifs bound by the transcription factor YY1 are associated with persistently accessible regulatory elements, including many promoters and enhancers of slow-silencing genes. We further show that YY1 is evicted relatively slowly from target sites on Xi, and that silencing of X-linked genes is increased upon YY1 degradation. Together our results suggest that YY1 acts as barrier to Xist-mediated silencing until late stages of the XCI process.
2024-02-28 | GSE244712 | GEO