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Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [CHART-seq]

ABSTRACT: Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [CHART-seq]

PROVIDER: PRJNA1194964 | ENA |

REPOSITORIES: ENA

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Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [CHART-seq]

Project description:Known to regulate chromosome looping on a genome-wide scale, the noncoding Jpx RNA was originally shown to control X-chromosome counting and induce Xist expression during X-chromosome inactivation (XCI). Not fully understood is how Jpx upregulates Xist in coordination with Tsix downregulation in cis. Here, by integrating epigenomic data and polymer modeling in a mouse embryonic stem cell model, we demonstrate that Jpx controls architectural and transcriptional dynamics within anti- and pro-XCI zones of the X-inactivation center. Distinct topological changes occur on the future active (Xa) and inactive (Xi) chromosomes. Jpx binds the enhancer of Tsix on the future Xi and alters loop formation to favor Xist induction, coordinately releasing CTCF from Tsix and Xist in cis on the future Xi. Thus, by controlling a dynamic rewiring of functional loops, Jpx flips a transcriptional switch to control mutually exclusive Tsix and Xist expression in cis.

2025-06-11 | GSE283642 | GEO

Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [RNA-Seq]

2025-06-11 | GSE283641 | GEO

Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [Capture Hi-C]

2025-06-11 | GSE225226 | GEO

Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center

Project description:Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center

| PRJNA1194957 | ENA

Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [RNA-Seq]

Project description:Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [RNA-Seq]

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Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [Capture Hi-C]

Project description:Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center [Capture Hi-C]

| PRJNA934376 | ENA

Species-specific regulation of XIST by the JPX/FTX orthologs

Project description:X chromosome inactivation (XCI) is a developmental regulatory process that initiates with remarkable diversity in various mammalian species. Here we addressed the contribution of XCI regulators, most of which are lncRNA genes (LRGs) characterized in the mouse, to this mechanistic diversity. By combining analysis of single-cell RNA-seq data from early human embryogenesis with various functional assays in pluripotent stem- and differentiated cells, we demonstrate that the function of Ftx is not conserved, while JPX stands a major regulator of XIST expression in human and in mouse. However, the underlying mechanisms differ radically between species and require Jpx RNA in the mouse and the act of transcription of the JPX locus in the human. Moreover, biogenesis of XIST is affected at different regulatory steps between these species. This study illustrates how diversification of LRG modus operanti during evolution provide opportunities for innovations within constrained gene regulatory networks.

2023-02-01 | GSE200317 | GEO

High-resolution chromosomal maps of Xist RNA reveal a two-step spreading mechanism during X-inactivation

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

Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-06-11 | GSE283643 | GEO

Species-specific regulation of XIST by the JPX/FTX orthologs

Project description:Species-specific regulation of XIST by the JPX/FTX orthologs

| PRJNA824048 | ENA