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Series GSE269349 Query DataSets for GSE269349
Status Public on Jun 07, 2024
Title PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression[CUT&RUN]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Genes encoding subunits of SWI/SNF chromatin remodeling complexes are mutated in nearly 25% of cancers. The SWI/SNF subunit SMARCB1 is the driving mutation in nearly all cases of rhabdoid tumor (RT), highly malignant cancers of childhood. While loss of SMARCB1 drives cancer, its absence also creates unique dependencies, which can illuminate mechanism and reveal potential therapeutic vulnerabilities. To identify such dependencies we undertook a genome-scale CRISPR screen comparing RT cell lines to 800 other cancer lines. We identified PHF6 as specifically essential for RT cell survival. Germline mutations in both SMARCB1 and PHF6 cause Coffin-Siris syndrome, and somatic mutations in PHF6 or SWI/SNF occur in T-ALL, suggesting a mechanistic link. We establish that PHF6 co-localizes with residual SWI/SNF complexes at active promoters and enhancers. We find that PHF6 is specifically required for H3K14ac accumulation immediately downstream of active promoters and for release of paused Pol II. Collectively, our work identifies novel integrated roles for PHF6 in chromatin and Pol II regulation, establishes a mechanistic basis for dependence upon PHF6 in RT, and reveals a novel potential therapeutic vulnerability in RT.
Overall design ChIP-Seq was performed in biological triplicate in either shPHF6 or non-targeting control for PHF6 antibody
Contributor(s) Mittal P, Roberts CW
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Submission date Jun 07, 2024
Last update date Jun 08, 2024
Contact name Jacquelyn A Myers
Organization name St. Jude Children’s Research Hospital
Street address 262 Danny Thomas Pl
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (4)
GSM8313568 DND41PHF6i_IgG_NA
GSM8313569 DND41PHF6i_IgG_DOX
GSM8313570 DND41PHF6i_PHF6ActiveMotif61807_DOX
This SubSeries is part of SuperSeries:
GSE180487 PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression
BioProject PRJNA1121263

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Supplementary file Size Download File type/resource
GSE269349_RAW.tar 309.7 Mb (http)(custom) TAR (of BW, NARROWPEAK)
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Raw data are available in SRA

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