The Mediator Kinase Complex Cooperates with Swi/Snf to Regulate Lineage-Resolved Enhancers and Differentiation [ChIP-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA789836 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17259026.fastq.gz | Fastqsanger.gz | |||
| SRR17259027.fastq.gz | Fastqsanger.gz | |||
| SRR17259028.fastq.gz | Fastqsanger.gz | |||
| SRR17259029.fastq.gz | Fastqsanger.gz | |||
| SRR17259030.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 11 |
Similar Datasets
Project description:The Mediator Kinase Complex Cooperates with Swi/Snf to Regulate Lineage-Resolved Enhancers and Differentiation
| PRJNA789825 | ENA
Project description:The Mediator Kinase Complex Cooperates with Swi/Snf to Regulate Lineage-Resolved Enhancers and Differentiation [RNA-Seq]
| PRJNA789835 | ENA
Project description: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.
2024-06-07 | GSE180481 | GEO
Project description: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.
2024-06-07 | GSE180486 | GEO
Project description:PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression
| PRJNA748399 | ENA
Project description:Here we performed transcriptional profiling of the prostate cancer cell lines LNCaP and 22Rv1 comparing non-targeting siRNA treatment versus siRNAs targeting SWI/SNF complex proteins (SMARCA2, SMARCA4, and SMARCB1). Goal was to determine the effect of SWI/SNF knockdown on gene expression in prostate cancer. Two-condition experiment: non-targeting siRNA versus SWI/SNF-siRNA treated cells. Three SWI/SNF proteins were targeted: SMARCA2, SMARCA4, and SMARB1. Biological replicates: 1 control replicate, 2 treatment replicates per SWI/SNF protein. Technical replicates: 1 replicate per SWI/SNF protein. Cell lines: 22Rv1 and LNCaP.
2013-07-20 | E-GEOD-40384 | biostudies-arrayexpress
Project description:A systems understanding of nuclear organization and events is critical for determining how cells divide, differentiate and respond to stimuli and for identifying the causes of diseases. Chromatin remodeling complexes such as SWI/SNF have been implicated in a wide variety of cellular processes including gene expression, nuclear organization, centromere function and chromosomal stability, and mutations in SWI/SNF components have been linked to several types of cancer. To better understand the biological processes in which chromatin remodeling proteins participate we globally mapped binding regions for several components of the SWI/SNF complex throughout the human genome using ChIP-Seq. SWI/SNF components were found to lie near regulatory elements integral to transcription (e.g. 5M-bM-^@M-^Y ends, RNA Polymerases II and III and enhancers) as well as regions critical for chromosome organization (e.g. CTCF, lamins and DNA replication origins). To further elucidate the association of SWI/SNF subunits with each other as well as with other nuclear proteins we also analyzed SWI/SNF immunoprecipitated complexes by mass spectrometry. Individual SWI/SNF factors are associated with their own family members as well as with cellular constituents such as nuclear matrix proteins, key transcription factors and centromere components implying a ubiquitous role in gene regulation and nuclear function. We find an overrepresentation of both SWI/SNF-associated regions and proteins in cell cycle and chromosome organization. Taken together the results from our ChIP and immunoprecipitation experiments suggest that SWI/SNF facilitates gene regulation and genome function more broadly and through a greater diversity of interactions than previously appreciated. ChIP-Seq analysis of the SWI/SNF subunits Ini1, Brg1, BAF155 and BAF170 in HeLa S3 cells
2011-01-10 | E-GEOD-24397 | biostudies-arrayexpress
Project description:Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of these complexes, physiological roles for this domain remain undefined. We screened an N-ethyl-N-nitrosurea (ENU) mutagenized library for ARID domain point mutations and generated an Arid1a/Baf250a hypomorphic allele. The mutant ARID1a (V1068G) protein is stably expressed at wild-type levels, and it is capable of assembling into a SWI/SNF complex with in vitro mononucleosome disruption activity. However, its capacity to bind DNA is lost. Consistent with defective DNA binding, mutant protein occupancy at known SWI/SNF target genes is decreased. Loss of DNA binding is associated with concurrent changes in SWI/SNF target gene expression. Mutant embryos manifest heart defects, fail to establish proper yolk sac vasculature, and exhibit hemorrhaging. As a result of these phenotypes, mutant embryos fail to establish proper circulation, culminating in ischemic arrest in utero between days 9.5 and 11.5. These data support a role for ARID1a-containing, BAF-A complexes in heart and extraembryonic vascular development, and indicate the ARID domain of ARID1a is essential in this regard. Hence, intrinsic ARID subunit-DNA interactions are required for normal SWI/SNF function in vivo. Four-condition experiment, wild-type vs Baf250a/Arid1a^V1068G/V1068G yolk sacs isolated at E8.5 and E9.5. Biological replicates: 3 per condition.
2012-01-15 | E-GEOD-32116 | biostudies-arrayexpress
Project description: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.
2024-06-07 | GSE180483 | GEO
Project description: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.
2024-06-07 | GSE269349 | GEO