|
| Status |
Public on Dec 31, 2017 |
| Title |
Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin [Atrx ChIP] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The chromatin regulator ATRX is inactivated in large subsets of adult and pediatric glioma. Whether and how ATRX deficiency promotes oncogenesis by epigenomic dysregulation remains unclear. We found that Atrx loss, especially when coupled with Tp53 inactivation, promoted cell motility and modulated differentiation state in primary murine neuroepithelial progenitors, recapitulating characteristic disease phenotypes and molecular features. Moreover, Atrx deficiency induced widespread shifts in chromatin accessibility, histone composition, and gene transcription at vacant Atrx binding sites distributed across the genome. Finally, target genes mediating Atrx-deficient phenotypes in vitro exhibited similarly selective misexpression in ATRX-mutant human glioma tissues and cell lines. These findings demonstrate that, in appropriate physiological contexts, ATRX deficiency and its epigenomic sequelae are sufficient to induce disease-defining oncogenic phenotypes.
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| |
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| Overall design |
Examination of ATRX binding sites in Tp53+/+ and Tp53-/- neuroepithelial progenitor cells (NPCs)
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| |
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| Contributor(s) |
Danussi C, Bose P, Kannan K, Huse J |
| Citation(s) |
29535300 |
| |
| Submission date |
Jun 26, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Jason T Huse |
| E-mail(s) |
jhuse@mdanderson.org
|
| Phone |
713-745-3186
|
| Organization name |
University of Texas MD Anderson Cancer Center
|
| Department |
Department of Pathology
|
| Street address |
1515 Holcombe Blvd
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE100465 |
Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin |
|
| Relations |
| BioProject |
PRJNA391902 |
| SRA |
SRP110502 |
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