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Series GSE66172 Query DataSets for GSE66172
Status Public on Mar 05, 2015
Title Effects of Firre knockdown on mouse gene expression
Organism Mus musculus x Mus spretus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design Examination of allelic expression in Patski cells upon Firre knockdown.
 
Contributor(s) Deng X, Yang F, Ma W, Noble WS, Shendure J, Disteche CM
Citation(s) 25887447, 26248554
Submission date Feb 20, 2015
Last update date Oct 09, 2019
Contact name Xinxian Deng
E-mail(s) dengx2@u.washington.edu
Organization name University of Washington
Department Laboratory Medicine and Pathology
Lab HSB C526
Street address 1959 NE Pacific St.
City Seattle
State/province WA
ZIP/Postal code 98195
Country USA
 
Platforms (1)
GPL16617 Illumina Genome Analyzer IIx (Mus musculus x Mus spretus)
Samples (4)
GSM1616196 Patski_control_rep1
GSM1616197 Patski_control_rep2
GSM1616198 Patski_FirreKD_rep1
This SubSeries is part of SuperSeries:
GSE59779 Studies of regulation of mouse X inactivation and genes escaping XCI
Relations
BioProject PRJNA276013
SRA SRP055391

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE66172_RAW.tar 1.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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