|
| Status |
Public on May 28, 2015 |
| Title |
Activation of proto-oncogenes by disruption of chromosome neighborhoods [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Mutations such as gene fusion, translocation and focal amplification are a frequent cause of proto-oncogene activation during tumorigenesis, but such mutations do not explain all cases of proto-oncogene activation. Here we show that disruption of local chromosome conformation can also activate proto-oncogenes in human cells. We mapped chromosome structures in T-cell acute lymphoblastic leukemia (T-ALL), and found that active oncogenes and silent proto-oncogenes generally occur within insulated neighborhoods formed by the looping of two interacting CTCF sites co-occupied by cohesin. Recurrent microdeletions frequently overlap neighborhood boundary sites in T-ALL genomes, and we demonstrate that site-specific perturbation of loop boundaries is sufficient to activate the respective proto-oncogenes in non-malignant cells. We found somatic genomic rearrangements affecting loop boundaries in many cancers. These results suggest that chromosome structural organization is fundamental to identify functional somatic alterations in cancer genomes.
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| |
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| Overall design |
CTCF ChIP-seq and input control in Jurkat T-ALL cells
H3K27Ac, RUNX1, and GATA3 ChIP-seq and input control in Jurkat T-ALL cells
CTCF ChIP-seq and input control in wildtype and mutant HEK293T cells
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| |
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| Contributor(s) |
Hnisz D, Weintraub AS, Fan ZP, Abraham BJ, Sigova AA, Reddy J, Lee TI, Young RA |
| Citation(s) |
26940867 |
| Submission date |
May 18, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
|
| Phone |
617-258-5219
|
| Organization name |
Whitehead Institute for Biomedical Research
|
| Lab |
Young Lab
|
| Street address |
9 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (10)
|
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| This SubSeries is part of SuperSeries: |
| GSE68978 |
Activation of proto-oncogenes by disruption of chromosome neighborhoods |
|
| Relations |
| BioProject |
PRJNA284251 |
| SRA |
SRP058436 |
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