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| Status |
Public on Jun 07, 2024 |
| Title |
PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Genes encoding subunits of SWI/SNF(BAF) chromatin remodeling complexes are collectively mutated in nearly 25% of all cancers. Utilizing a genome-wide CRISPR-Cas9 screen, we identify PHF6 as a specific vulnerability in pediatric malignant rhabdoid tumors (RTs), which are driven by inactivation of the SMARCB1 subunit of SWI/SNF. We establish that PHF6 co-localizes with residual SWI/SNF subcomplexes at promoters and enhancers. Here, PHF6 facilitates transcriptional activation by regulating deposition of H3K14ac downstream of active promoters and contributes to the establishment of H3K27ac at active promoters and enhancers. We show that PHF6 is essential for the maintenance of these marks in part via the regulation of their writers, HB01 and CBP/p300, respectively. As it directly regulates the H3K14ac mark, PHF6 may regulate pausing and serve as a mediator between chromatin regulatory function and RNA POL II pause release. Together, our results establish a mechanistic basis for dependence upon PHF6 in SMARCB1-mutant RTs.
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| Overall design |
RNA-Seq was performed using 9 biological replicates of G401 shCTRL (control) and 11 biological replicates for shPHF6 (experimental).
RNA-Seq was performed using 3 biological replicates of MRT cell lines upon loss of PHF6 or BRD9 (via shRNAs) compared to controls
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| Contributor(s) |
Mittal P, Roberts CW |
| Citation(s) |
39181868 |
| |
| Submission date |
Jul 20, 2021 |
| Last update date |
Sep 06, 2024 |
| Contact name |
Jacquelyn A Myers |
| E-mail(s) |
jamyers2358@gmail.com
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| Organization name |
St. Jude Children’s Research Hospital
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| Street address |
262 Danny Thomas Pl
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (38)
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| This SubSeries is part of SuperSeries: |
| GSE180487 |
PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression |
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| Relations |
| BioProject |
PRJNA748393 |
| SRA |
SRP329125 |
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