|
| Status |
Public on Apr 26, 2017 |
| Title |
Non-overlapping control of transcriptome by Promoter and Super-Enhancer-Associated Dependencies |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The relationship between promoter proximal transcription factor-associated gene expression and super-enhancer-driven transcriptional programs are not well-defined. Some level of their distinct genomic occupancy may suggest a mechanism with specific target gene control. We explored the transcriptional and functional interrelationship between E2F transcription factors and BET transcriptional co-activators in multiple myeloma. Global chromatin analysis reveals distinct regulatory axes for E2F and BETs, with E2F predominantly localized to active gene promoters of growth/proliferation genes and BETs disproportionately at enhancer- regulated tissue specific genes. Depletion of E2F selectively down-regulates its regulatory axis and is generally synergistic with BET inhibition. In vivo, combined inhibition of BETs and E2F strongly reduces tumor growth, implicating E2F as a myeloma dependency that is potently leveraged with BET inhibition.
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| |
|
| Overall design |
ChIP-Seq in U266 and MM1.S multiple myeloma cell lines
|
| |
|
| Contributor(s) |
Munshi NP, Fulciniti M, Lin CY |
| Citation(s) |
30590042 |
| Submission date |
Apr 26, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Nikhil C Munshi |
| E-mail(s) |
nikhil_munshi@dfci.harvard.edu
|
| Phone |
617-632-4218
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Hematologic Oncology
|
| Street address |
450 Brookline Avenue
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA319620 |
| SRA |
SRP073902 |
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