Unfolding the inactive X chromosome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA478454 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7451430_1.fastq.gz | Fastqsanger.gz | |||
| SRR7451430_2.fastq.gz | Fastqsanger.gz | |||
| SRR7451431_1.fastq.gz | Fastqsanger.gz | |||
| SRR7451431_2.fastq.gz | Fastqsanger.gz | |||
| SRR7451423_1.fastq.gz | Fastqsanger.gz |
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Project description:The inactive X chromosome (Xi) is folded in a stepwise process into a compartment-less structure. Here we investigate if the Xi can be unfolded in post-XCI cells. We began with ablating structural maintenance of chromosomes hinge domain containing 1 (Smchd1) in female mouse embryonic fibroblasts (MEFs), a cell type in which XCI is completed. We then performed in situ Hi-C on one Smchd1+/+ (wild-type, WT) and one Smchd1-/- (knockout, KO) MEF clone to probe the role of SMCHD1 in maintaining the higher-order structure of the Xi. To determine if the change in chromosome structure is accompanied by altered gene expression, we performed RNA-seq on two WT and two independently generated Smchd1-/- clones treated with either DMSO or 5-aza-2'-deoxycytidine (Aza), a DNA demethylating agent. In addition, we performed H3K27me3 and H2AK119ub ChIP-seq and Xist Capture Hybridization Analysis of RNA Targets with deep sequencing (CHART-seq) on one WT and one Smchd1-/- MEF clone to determine if there is an alteration in the epigenetic state of the Smchd1-/- Xi. Finally, we examined the role of Xist, Polycomb repressive complex 1 (PRC1), and Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) in regulating the Xi structure in post-XCI cells. To do so we performed in situ Hi-C on WT and Smchd1-/- MEFs depleted with either PRC1 or HNRNPK, as well as on fibroblasts in which Xist is deleted on the Xi (XidelXist).
2019-05-03 | GSE116413 | GEO
Project description:3D-topology of DNA in the cell nucleus provides a level of transcription regulation beyond the sequence of the linear DNA. To study the relationship between transcriptional activity and spatial environment of a gene, we have used allele-specific 4C-technology to produce high-resolution topology maps of the active and inactive X-chromosomes in female cells. We found that loci on the active X form multiple long-range interactions, with spatial segregation of active and inactive chromatin. On the inactive X, silenced loci lack preferred interactions, suggesting a unique random organization inside the inactive territory. However, escapees, among which is Xist, are engaged in long-range contacts with each other, enabling identification of novel escapees. Deletion of Xist results in partial re-folding of the inactive X into a conformation resembling the active X, without affecting gene silencing or DNA methylation. Our data point to a role for Xist RNA in shaping the conformation of the inactive X-chromosome independently of transcription. Five or six 4C viewpoints were applied on the mouse female wild type active X-chromosome, the wild type inactive X-chromosome, the conditional Xist X-chromosome and the Xist knock out X-chromosome
2011-06-24 | E-GEOD-29509 | biostudies-arrayexpress
Project description:Using long-read nanopore sequencing, we obtained chromosome-wide phased methylomes of the active and inactive X in mouse placenta and neural stem cells (NSCs), overcoming the limitations if short-read bisulfite sequencing in allelic resolution. We also conducted quantitative analysis of methylation properties like symmetry and entropy, providing a more comprehensive view of epigenetic silencing in X chromosome inactivation. We also resolved the allele-specific genetics and epigenetics of structural macrosatellite Dxz4 and other repeats.
2024-03-12 | E-MTAB-13706 | biostudies-arrayexpress
Project description:In mammals, genes located on the X chromosome are present in one copy in XY males and two in XX females. To balance the dosage of X-linked gene expression between the sexes one of the two X chromosomes in females is silenced by X inactivation initiated by up-regulation of the lncRNA (long non-coding RNA) Xist and recruitment of specific chromatin modifiers for silencing. The inactivated X chromosome becomes heterochromatic and visits a specific nuclear compartment adjacent to the nucleolus. We report a novel role for the X-linked lncRNA Firre in anchoring the inactive mouse X chromosome and preserving one of its main epigenetic features, trimethylation of histone H3 at lysine 27 (H3K27me3). Similar to Dxz4, Firre is expressed from a macrosatellite repeat locus associated with a cluster of CTCF and cohesin binding specifically on the inactive X. CTCF binding initially present in both male and female mouse embryonic stem cells was found to be lost from the active X during development. The Firre and Dxz4 loci on the inactive X were preferentially located adjacent to the nucleolus. Knockdown of Firre RNA disrupted perinucleolar targeting and H3K27me3 levels in mouse fibroblasts, demonstrating an important role for this lncRNA in maintenance of one of the main epigenetic features of the X chromosome. There was no X-linked gene reactivation after Firre knockdown; however, a compensatory increase in the expression of chromatin modifier genes implicated in X silencing was observed. In female ES cells Firre RNA knockdown did not disrupt Xist expression/coating nor silencing of G6pdx during differentiation, suggesting that Firre does not play a role in the onset of X inactivation. We conclude that the X-linked lncRNA Firre helps position the inactive X chromosome near the nucleolus and preserve one of its main epigenetic features.
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Project description:Comparison of human iPSC lines, ESC and fibroblasts to determine their expression patterns. All early passage female lines profiled expressed XIST RNA which is an indicator of an inactive X chromosome. Genes on the X-chromosome were also analyzed for overall levels of gene expression compared to human fibroblasts.
2010-08-19 | GSE22246 | GEO
Project description:Whole-chromosome methylation patterns of the mouse inactive X
| PRJEB71972 | ENA
Project description:Comparison of human iPSC lines, ESC and fibroblasts to determine their expression patterns. All early passage female lines profiled expressed XIST RNA which is an indicator of an inactive X chromosome. Genes on the X-chromosome were also analyzed for overall levels of gene expression compared to human fibroblasts. hiPSC lines were generated and extracted for RNA with TriZOL and hybridization on Affymetrix arrays.
2010-08-18 | E-GEOD-22246 | biostudies-arrayexpress
Project description:In mammals, genes located on the X chromosome are present in one copy in XY males and two in XX females. To balance the dosage of X-linked gene expression between the sexes one of the two X chromosomes in females is silenced by X inactivation initiated by up-regulation of the lncRNA (long non-coding RNA) Xist and recruitment of specific chromatin modifiers for silencing. The inactivated X chromosome becomes heterochromatic and visits a specific nuclear compartment adjacent to the nucleolus. We report a novel role for the X-linked lncRNA Firre in anchoring the inactive mouse X chromosome and preserving one of its main epigenetic features, trimethylation of histone H3 at lysine 27 (H3K27me3). Similar to Dxz4, Firre is expressed from a macrosatellite repeat locus associated with a cluster of CTCF and cohesin binding specifically on the inactive X. CTCF binding initially present in both male and female mouse embryonic stem cells was found to be lost from the active X during development. The Firre and Dxz4 loci on the inactive X were preferentially located adjacent to the nucleolus. Knockdown of Firre RNA disrupted perinucleolar targeting and H3K27me3 levels in mouse fibroblasts, demonstrating an important role for this lncRNA in maintenance of one of the main epigenetic features of the X chromosome. There was no X-linked gene reactivation after Firre knockdown; however, a compensatory increase in the expression of chromatin modifier genes implicated in X silencing was observed. In female ES cells Firre RNA knockdown did not disrupt Xist expression/coating nor silencing of G6pdx during differentiation, suggesting that Firre does not play a role in the onset of X inactivation. We conclude that the X-linked lncRNA Firre helps position the inactive X chromosome near the nucleolus and preserve one of its main epigenetic features. Examination of allelic protein-binding or histone modification profiles in Patski cells.
2015-02-26 | E-GEOD-66262 | biostudies-arrayexpress
Project description:3D-topology of DNA in the cell nucleus provides a level of transcription regulation beyond the sequence of the linear DNA. To study the relationship between transcriptional activity and spatial environment of a gene, we have used allele-specific 4C-technology to produce high-resolution topology maps of the active and inactive X-chromosomes in female cells. We found that loci on the active X form multiple long-range interactions, with spatial segregation of active and inactive chromatin. On the inactive X, silenced loci lack preferred interactions, suggesting a unique random organization inside the inactive territory. However, escapees, among which is Xist, are engaged in long-range contacts with each other, enabling identification of novel escapees. Deletion of Xist results in partial re-folding of the inactive X into a conformation resembling the active X, without affecting gene silencing or DNA methylation. Our data point to a role for Xist RNA in shaping the conformation of the inactive X-chromosome independently of transcription.
2011-06-24 | GSE29509 | GEO
Project description:Whether RNA G-quadruplexes (rG4) form extensively in vivo and what roles they play remain actively debated. Among their proposed functions is recognition of Polycomb repressive complex 2 (PRC2), but how the interaction results in epigenetic regulation is not understood. Here we demonstrate that rG4s form dynamically during ES cell differentiation and require ATRX’s helicase function to unwind competing secondary structures. Mutating ATRX causes rG4 depletion on a transcriptome-wide basis and dramatically increases gene expression. We identify and mutate rG4s within Xist RNA and mechanistically separate PRC2’s recruitment versus catalysis. Surprisingly, although rG4s recruit PRC2, unfolding the rG4 structure causes PRC2 hyperactivation, entrapment of PRC2 in the S1 chromosomal compartment, and loss of gene silencing. Thus, we link dynamic rG4 folding and unfolding to PRC2 recruitment, trans-compartmental Xist migration, regulated activation of PRC2, and whole-chromosome gene silencing.
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