Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Trans- and cis-acting effects of the lncRNA Firre on epigenetic and structural features of the inactive X chromosome [ChIP-seq]

ABSTRACT: Firre encodes a lncRNA involved in nuclear organization in mammals. Here we find that Firre RNA is transcribed from the active X chromosome (Xa) and exerts trans-acting effects on the inactive X chromosome (Xi). Allelic deletion of Firre on the Xa in a mouse hybrid fibroblast cell line results in a dramatic loss of the histone modification H3K27me3 and of components of the PRC2 complex on the Xi as well as the disruption of the perinucleolar location of the Xi. These features are measurably rescued by ectopic expression of a mouse or human Firre/FIRRE cDNA transgene, strongly supporting a conserved trans-acting role of the Firre transcript in maintaining the Xi heterochromatin environment. Surprisingly, CTCF occupancy is decreased on the Xi upon loss of Firre RNA, but is partially recovered by ectopic transgene expression, suggesting a functional link between Firre RNA and CTCF in maintenance of epigenetic features and/or location of the Xi. Loss of Firre RNA results in dysregulation of genes implicated in cell division and development, but not in reactivation of genes on the Xi, which retains its bipartite structure despite some changes in chromatin contact distribution. Allelic deletion or inversion of Firre on the Xi causes localized redistribution of chromatin contacts, apparently dependent on the orientation of CTCF binding sites clustered at the locus. Thus, the Firre locus and its RNA have roles in the maintenance of epigenetic features and structure of the Xi.

ORGANISM(S): Mus musculus x Mus spretus

PROVIDER: GSE134305 | GEO | 2020/05/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Effects of Firre knockdown on mouse gene expression

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 expression in Patski cells upon Firre knockdown.

2015-03-05 | E-GEOD-66172 | biostudies-arrayexpress

Female-specific CTCF binding on the inactive X chromosome in mouse

2015-02-26 | E-GEOD-66262 | biostudies-arrayexpress

Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation.

Project description:X-chromosome inactivation (XCI) achieves dosage compensation between males and females through the silencing of the majority of genes on one X chromosome, with approximately 15% of genes reported to show inactive X (Xi) expression. We examined the interplay between ChromHMM states, CpG density, expression and DNAm from over 1800 female samples with the Illumina 450K array. The interaction between CpG density and histone marks differed between the active X (Xa) and the Xi, with X-linked promoters reflecting transcriptional status, while the Xi showed lower DNAm than the Xa at all non-promoter regions. Promoter DNAm was used to determine a novel XCI status for more than 100 transcription start sites and a comparison across 27 tissues revealed the majority of genes were consistently subject to XCI. Inter-female and twin data supported a model of predominately cis-acting influences on escape, or variable escape, from XCI. Increased promoter DNAm at escape genes correlated with decreased relative Xi expression up to ~15% female DNAm but above this threshold DNAm was not correlated with the stability of silencing. Xi DNAm was ~12% lower than Xa DNAm within the gene bodies of subject genes and between genes while there was equivalent DNAm at escape genes. In addition to offering insight into sex-specific difference in disease, female X chromosomes provide the opportunity to compare euchromatin and heterochromatin of allelic regions within the same nuclear environment and demonstrate the correlation of DNAm with transcription and the influences of CpG density and chromatin marks.

2014-11-29 | GSE60275 | GEO

Xi-reactivation in female human induced pluripotent stem cells (hiPSCs)

Project description:Female human induced pluripotent stem cell (hiPSC) lines exhibit considerable variability in X-inactivation status. Some lines maintain one transcriptionally active X chromosome (Xa) and one inactive X (Xi) from donor cells. However, hiPSC lines that have two Xas are infrequently produced. We show here Xinactivation status in female hiPSC lines depends on derivation conditions. hiPSC lines generated using the Kyoto method, which employs leukemia inhibitory factor (LIF)-expressing SNL feeders, frequently had two Xas. Lines derived on other feeders maintained an Xi. In addition, there appears to be a window in which SNL feeders promote Xi-reactivation. Upon differentiation, Xa/Xa hiPSCs silenced one X. The efficient production of Xa/Xa hiPSC lines provides unprecedented opportunities to understand human X-reactivation and inactivation.

2013-02-06 | GSE44044 | GEO

Female human induced pluripotent stem cells (hiPSCs)

2012-07-06 | GSE34527 | GEO

Megadomains and superloops form dynamically during X-chromosome inactivation but are dispensable for silencing and escape

Project description:The mammalian inactive X-chromosome (Xi) is structurally distinct from all other chromosomes and serves as a model for higher order chromosome organization. The Xi lacks strong topologically associated domains and is instead organized into megadomains and superloops mediated in part by the noncoding loci, Dxz4 and Firre. Their functional significance is presently unclear, though one study suggests that they permit Xi genes to escape silencing. Here, we find that megadomains do not form before silencing spreads along the Xi. Deletional analysis shows that Dxz4, but not Firre, is required for megadomains. Surprisingly, however, deleting neither Dxz4 nor Firre impacts Xi silencing or gene escape. Nor does it affect Xi nuclear localization, stability, or H3K27 methylation. Furthermore, ectopic integration of Dxz4 and Xist is not sufficient to form megadomains on autosomes, thereby uncoupling megadomain formation from chromosomal silencing. We conclude that Dxz4 and megadomains are dispensable for Xi silencing and escape.

2018-10-31 | GSE116649 | GEO

Escape from X inactivation in mouse tissues (RNA-Seq)

Project description:X chromosome inactivation (XCI) silences most genes on one X chromosome in female mammals, but some genes escape XCI. To identify escape gene in vivo and to explore molecular mechanisms that regulate this process we analyzed the allele-specific expression and chromatin structure of X-linked genes in mouse tissues and cells with skewed XCI and distinguishable alleles based on single nucleotide polymorphisms. Using a new method to estimate allelic expression, we demonstrate a continuum between complete silencing and significant expression from the inactive X (Xi). Few genes (2-3%) escape XCI to a significant level and only a minority differs between mouse tissues, suggesting stringent silencing and escape controls. Allelic profiles of DNase I hypersensitivity and RNA polymerase II occupancy of genes on the Xi correlate with escape from XCI. Allelic binding profiles of the DNA binding protein CCCTC-binding factor (CTCF) in different cell types indicate that CTCF binding at the promoter correlates with escape. Importantly, CTCF binding at the boundary between escape and silenced domains may prevent the spreading of active escape chromatin into silenced domains. Examination of allelic expression in mouse hybrid tissues.

2015-02-20 | E-GEOD-59777 | biostudies-arrayexpress

Escape from X inactivation in mouse tissues (ChIP-Seq)

2015-02-20 | E-GEOD-59778 | biostudies-arrayexpress

Female human induced pluripotent stem cells (hiPSCs)

2012-07-06 | E-GEOD-34527 | biostudies-arrayexpress

Xi-reactivation in female human induced pluripotent stem cells (hiPSCs)

2013-02-06 | E-GEOD-44044 | biostudies-arrayexpress