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| Status |
Public on Jan 08, 2018 |
| Title |
A TFIID-SAGA perturbation that targets MYB and suppresses acute myeloid leukemia (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Targeting of general coactivators, such as BRD4, is an emerging strategy to interfere with oncogenic transcription factors (TFs) in cancer. However, coactivator perturbations have the potential to influence the function of numerous TFs, thereby resulting in biological pleiotropy. Here we identify TAF12, an 18 kilodalton subunit of TFIID/SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia (AML) progression. We trace this AML-specific dependency to a direct interaction between the TAF12/TAF4 histone-fold heterodimer and the transactivation domain of MYB, a TF with established roles in leukemogenesis. Ectopic expression of a histone-fold domain fragment of TAF4 can efficiently squelch TAF12 in cells, suppress MYB, and regress AML in mice. Our study reveals a strategy for potent MYB inhibition in AML and highlights how an oncogenic TF can be selectively neutralized by targeting a general coactivator complex.
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| Overall design |
TAF2 and TAF10 ChIP-seq were performed using antibodies recognizing endogenous protein with input genomic DNA as control. FLAG-TAF12 ChIP-seq was performed in FLAG-TAF12 expressing cells.
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| Contributor(s) |
Xu Y, Vakoc CR |
| Citation(s) |
29316427 |
| |
| Submission date |
Sep 27, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Yali XU |
| E-mail(s) |
yxu@cshl.edu
|
| Organization name |
Cold Spring Harbor Laboratory
|
| Street address |
1 Bungtown Road
|
| City |
Cold Spring Harbor |
| State/province |
NY |
| ZIP/Postal code |
11724 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE104309 |
A TFIID-SAGA perturbation that targets MYB and suppresses acute myeloid leukemia |
|
| Relations |
| BioProject |
PRJNA412431 |
| SRA |
SRP119046 |
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