|
| Status |
Public on Feb 26, 2015 |
| Title |
Female-specific CTCF binding on the inactive X chromosome in mouse |
| Platform organism |
Mus musculus |
| Sample organisms |
Mus musculus; Mus musculus x Mus spretus |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
|
| 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.
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| |
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| Overall design |
Examination of allelic protein-binding or histone modification profiles in Patski cells.
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| |
|
| Contributor(s) |
Yang F, Deng X, Disteche CM |
| Citation(s) |
25887447, 26248554 |
| Submission date |
Feb 24, 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 (5)
|
| GPL10129 |
NimbleGen Mouse 2.1 M array 10 of 10 |
| GPL13603 |
NimbleGen Mouse 2006-07-17_MM8Tiling_Set37 [DESIGN_ID: 4108] |
| GPL13604 |
NimbleGen Mouse 2006-07-17_MM8Tiling_Set38 [DESIGN_ID: 4109] |
| GPL16733 |
NimbleGen Mus musculus 2.1M 2007-09-21_MM8_Deluxe_Promoter_HX1 tiling design |
| GPL16743 |
Agilent-028383 SurePrint G3 Mouse Promoter Microarray 1x1M |
|
| Samples (19)
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| This SubSeries is part of SuperSeries: |
| GSE59779 |
Studies of regulation of mouse X inactivation and genes escaping XCI |
|
| Relations |
| BioProject |
PRJNA276479 |
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