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| Status |
Public on Jul 16, 2015 |
| Title |
Bipartite structure of the inactive mouse X chromosome |
| Organism |
Mus musculus x Mus spretus |
| Experiment type |
Other
|
| Summary |
A subset of genomic regions, including one of the female X chromosomes and all imprinted genes, are expressed exclusively from a single allele in somatic cells of mammals. To evaluate structural changes associated with allelic silencing, we used mouse F1 hybrid systems in which X inactivation is skewed and alleles can be distinguished based on single nucleotide polymorphisms to analyze chromatin contacts by a new Hi-C assay that uses DNase I for chromatin fragmentation. Both DNase Hi-C and in situ DNase Hi-C reveal a radically different conformation between the two female mouse X chromosomes. Two superdomains of frequent intrachromosomal contacts separated by a hinge region are specifically observed on the inactive X chromosome both in vivo (brain) and in vitro (Patski cells). A bipartite 3D organization of the inactive X has been also reported in human lymphoblastoid cells, suggesting that this conserved structure probably plays an important role in maintenance of gene silencing on the inactive X. Interestingly, we found that the genomic content of the superdomains differs between species, but that part of the hinge region is conserved and located near the Dxz4/DXZ4 locus that binds CTCF on the inactive X. In mouse, the hinge region also contains a minisatellite Ds-TR adjacent to a promoter with strong CTCF binding. Both Dxz4 and Ds-TR bind nucleophosmin and are enriched in nucleolus-associated chromatin, suggesting anchoring to the nucleolus. Genes that escape X inactivation do not cluster but are preferentially located near the periphery of the 3D structure. Regions enriched in CTCF or RNA polymerase are also preferentially located on the periphery of the inactive X while LINE1 elements are preferentially on the interior. Genes subject to silencing exhibit fewer detectable intrachromosomal contacts than escape genes. This transcription-coupled pattern is also evident for imprinted genes, in which more chromatin contacts are detected on the expressed allele, suggesting greater constraint on the organization of expressed genomic regions.
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| |
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| Overall design |
DNase Hi-C assay and in situ Dnase Hi-C assay in F1 hybrid mouse brain and Patski cells
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| Contributor(s) |
Deng X, Ma W, Ramani V, Shendure J, Duan Z, Noble WS, Disteche C |
| Citation(s) |
25887447, 26248554 |
| |
| Submission date |
May 18, 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 |
| |
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| Platforms (2) |
| GPL16616 |
Illumina HiSeq 2000 (Mus musculus x Mus spretus) |
| 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 |
PRJNA284392 |
| SRA |
SRP058499 |
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