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| Status |
Public on Nov 28, 2017 |
| Title |
An evaluation of the effects of CRISPR/cas9-mediated editing of the Dxz4 locus on regulation of the mouse inactive X chromosome in Patski cells [ATAC-seq] |
| Organism |
Mus musculus x Mus spretus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts separated by a boundary or hinge region. Using in situ DNase Hi-C in mouse cells with deletions or inversions within the hinge, we show that the conserved repeat locus Dxz4 alone is sufficient to maintain the bipartite structure and that Dxz4 orientation controls the distribution of long-range contacts on the Xi. Frequent long-range contacts between Dxz4 and the telomeric superdomain are either lost after its deletion or shifted to the centromeric superdomain after its inversion. This massive reversal in contact distribution is consistent with the reversal of CTCF motif orientation at Dxz4. Decondensation of the Xi after Dxz4 deletion is associated with partial restoration of TADs normally attenuated on the Xi, and with an increase in chromatin accessibility and CTCF binding, but few changes in gene expression, in accordance with multiple epigenetic mechanisms ensuring X silencing. We propose that Dxz4 represents a structural platform for frequent long-range contacts with multiple loci in a direction dictated by the orientation of a bank of CTCF motifs at Dxz4, which may work as a ratchet to form the distinctive bipartite structure of the condensed Xi.
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| Overall design |
ATAC-seq experiment on F1 hybrid wild-type and CRISPR/cas9-modified Patski cells.
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| Contributor(s) |
Bonora G, Deng X, Fang H, Ramani V, Qui R, Berletch J, Filippova GN, Duan Z, Shendure J, Noble WS, Disteche C |
| Citation(s) |
29654302, 26248554 |
| Submission date |
Nov 22, 2017 |
| 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) |
| GPL20213 |
Illumina NextSeq 500 (Mus musculus x Mus spretus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE59779 |
Studies of regulation of mouse X inactivation and genes escaping XCI |
|
| Relations |
| BioProject |
PRJNA419574 |
| SRA |
SRP125519 |
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