Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA341274 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4101256_1.fastq.gz | Fastqsanger.gz | |||
| SRR4101256_2.fastq.gz | Fastqsanger.gz | |||
| SRR4101257_1.fastq.gz | Fastqsanger.gz | |||
| SRR4101257_2.fastq.gz | Fastqsanger.gz | |||
| SRR4101258_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing
| PRJNA319159 | ENA
Project description:Xist orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the 3-dimensional structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here we show that Xist directly interacts with the Lamin B Receptor (LBR), an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing. We show that this interaction recruits the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the accessibility of DNA thereby enabling Xist, and its silencing proteins, to spread across the X to silence transcription. We examined the genomic localization of the Xist lncRNA using RNA Antisense Purification (RAP) in male mouse ES cells where the endogenous Xist promoter is replaced by a tet-inducible one (pSM33) containing 1) wild-type Xist (WT), 2) A-repeat deletion Xist (dA), 3) LBR binding site deletion Xist (dLBS), 4) dLBS-Xist rescued with LMNB1 (LMNB1Res), 5) LBR CRISPRi knock down (LBRKD), or 6) SHARP CRISPRi knock down (SHARPKD).
2016-07-24 | E-GEOD-80510 | biostudies-arrayexpress
Project description:Xist orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the 3-dimensional structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here we show that Xist directly interacts with the Lamin B Receptor (LBR), an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing. We show that this interaction recruits the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the accessibility of DNA thereby enabling Xist, and its silencing proteins, to spread across the X to silence transcription.
2016-09-02 | GSE86250 | GEO
Project description:Xist orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the 3-dimensional structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here we show that Xist directly interacts with the Lamin B Receptor (LBR), an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing. We show that this interaction recruits the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the accessibility of DNA thereby enabling Xist, and its silencing proteins, to spread across the X to silence transcription.
2016-07-24 | GSE80510 | GEO
Project description:At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in the initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen-/- ESCs can be rescued by concomitant removal of Tsix. These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in the initiation of the XCI process.
2021-09-30 | GSE163320 | GEO
Project description:At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in the initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen-/- ESCs can be rescued by concomitant removal of Tsix. These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in the initiation of the XCI process.
2021-09-30 | GSE163319 | GEO
Project description:To initiate X-chromosome inactivation (XCI), the long non-coding RNA Xist mediates chromosome-wide gene silencing of one X chromosome in female mammals to equalize gene dosage between the sexes. The efficiency of gene silencing, however is highly variable across genes, with some genes even escaping XCI in somatic cells. A gene’s susceptibility to Xist-mediated silencing appears to be determined by a complex interplay of epigenetic and genomic features; however, the underlying rules remain poorly understood. We have quantified chromosome-wide gene silencing kinetics at the level of the nascent transcriptome using allele-specific Precision nuclear Run-On sequencing (PRO-seq). We have developed a Random Forest machine learning model that can predict the measured silencing dynamics based on a large set of epigenetic and genomic features and tested its predictive power experimentally. While the genomic distance to the Xist locus is the prime determinant of the speed of gene silencing, we find that also pre-marking of gene promoters with polycomb complexes is associated with fast silencing. Moreover, a series of features associated with active transcription and the O-GlcNAc transferase Ogt are enriched at rapidly silenced genes. Our machine learning approach can thus uncover the complex combinatorial rules underlying gene silencing during X inactivation.
2019-06-06 | GSE121144 | GEO
Project description:Xist is indispensable for X chromosome inactivation (XCI) in female mammalian cells. However, how Xist RNA directs chromosome-wide transcriptional inactivation of the X chromosome is largely unknown. Here, to study chromosome inactivation by Xist, we generated a system where ectopic Xist expression can be induced from several genomic contexts in aneuploid mouse ES cells. We found that ectopic Xist expression from any location on the X chromosome faithfully recapitulated endogenous XCI, showing the potency of Xist to initiate XCI. Genes that escape XCI remain consistently transcriptionally active upon ectopic XCI, regardless of their position relative to Xist transgenes, and the enrichment of CTCF at their promoters is implicated in directing XCI escape. Xist expression from autosomes facilitates their transcriptional silencing to different degrees, and gene density in proximity of the Xist transcription locus plays a central role in determining the efficiency of gene inactivation. We also show that the enrichment of LINE elements together with a specific chromatin environment facilitates Xist-mediated silencing of both X-linked and autosomal genes. These findings provide new insights into the epigenetic mechanisms that mediate XCI and identify genomic features that promote Xist-mediated chromosome-wide gene inactivation
2017-07-04 | GSE92894 | GEO
Project description:The long non-coding RNA Xist exploits numerous effector proteins to gradually induce gene silencing across the X chromosome. Here, we show that formation of the inactive X (Xi)-compartment is induced by ~50 locally confined granules, where two Xist RNA molecules nucleate supra-molecular complexes (SMCs) of interacting proteins. Xist-SMCs are dynamic structures that concentrate rapidly recycling proteins on the X by increasing their binding affinity, thereby facilitating their access to the entire chromosome. We find that gene silencing originates at Xist-SMCs and propagates across the entire X chromosome over time. The propagation of silencing is achieved by Polycomb-mediated coalescence of chromatin regions and aggregation of the critical silencing enzyme SPEN, via its intrinsically disordered domains. Our observations suggest a new model for X Chromosome Inactivation, whereby Xist RNA triggers macromolecular crowding of heterochromatinizing proteins at distinct sites to ultimately increase their occupancy throughout the X chromosome . This mechanism enables deterministic gene silencing across an entire chromosome without the need for Xist ribonucleoprotein complex-chromatin interactions at each target gene. Our findings uncover a spatial organization mechanism by which few RNA molecules can regulate a broad nuclear compartment through the recruitment and local concentration of dynamic effector proteins, and provide a quantitative framework for studying such compartments.
2021-10-27 | GSE162011 | GEO
Project description:The long non-coding RNA Xist exploits numerous effector proteins to gradually induce gene silencing across the X chromosome. Here, we show that formation of the inactive X (Xi)-compartment is induced by ~50 locally confined granules, where two Xist RNA molecules nucleate supra-molecular complexes (SMCs) of interacting proteins. Xist-SMCs are dynamic structures that concentrate rapidly recycling proteins on the X by increasing their binding affinity, thereby facilitating their access to the entire chromosome. We find that gene silencing originates at Xist-SMCs and propagates across the entire X chromosome over time. The propagation of silencing is achieved by Polycomb-mediated coalescence of chromatin regions and aggregation of the critical silencing enzyme SPEN, via its intrinsically disordered domains. Our observations suggest a new model for X Chromosome Inactivation, whereby Xist RNA triggers macromolecular crowding of heterochromatinizing proteins at distinct sites to ultimately increase their occupancy throughout the X chromosome. This mechanism enables deterministic gene silencing across an entire chromosome without the need for Xist ribonucleoprotein complex-chromatin interactions at each target gene. Our findings uncover a spatial organization mechanism by which few RNA molecules can regulate a broad nuclear compartment through the recruitment and local concentration of dynamic effector proteins, and provide a quantitative framework for studying such compartments.
2021-10-27 | GSE181235 | GEO