|
| Status |
Public on Mar 20, 2018 |
| Title |
Chromosome loop control of oncogenic MYC produces a common vulnerability in diverse cancers [HiChIP] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The majority of human cancers become highly dependent on a deregulated MYC oncogene, thus identifying a common mechanism underlying MYC regulation could provide valuable targets for therapy. We show here that diverse tumor-specific super-enhancers acquired throughout the 3Mb MYC insulated neighborhood functionally interact with a single conserved site occupied by CTCF protein in the MYC promoter. CRISPR-mediated deletion analysis shows that this common CTCF site is required for super-enhancer looping to the MYC promoter, high MYC expression and rapid cell proliferation in multiple cancers. Targeted methylation of the MYC enhancer anchor by a dCAS9-DNMT3A-3L fusion protein abrogates CTCF binding with consequent loss of MYC expression, suggesting a common vulnerability and a novel approach for therapeutic targeting of aggressive cancers.
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| |
|
| Overall design |
Evaluation of SMC1 loops in human colorectal cancer cell line
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| |
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| Contributor(s) |
Schuijers J |
| Citation(s) |
29641996 |
| |
| Submission date |
Mar 19, 2018 |
| Last update date |
Mar 27, 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 |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (1) |
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| This SubSeries is part of SuperSeries: |
| GSE92881 |
Chromosome loop control of oncogenic MYC produces a common vulnerability in diverse cancers |
|
| Relations |
| BioProject |
PRJNA438926 |
| SRA |
SRP135985 |
