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A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation [RNA-seq]

ABSTRACT: A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation [RNA-seq]

PROVIDER: PRJNA449854 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6987820.fastq.gz	Fastqsanger.gz
	SRR6987830.fastq.gz	Fastqsanger.gz
	SRR6987811.fastq.gz	Fastqsanger.gz
	SRR6987821.fastq.gz	Fastqsanger.gz
	SRR6987831.fastq.gz	Fastqsanger.gz

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Similar Datasets

A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation

Project description:A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation

| PRJNA449852 | ENA

A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation [ChIP-seq]

Project description:A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation [ChIP-seq]

| PRJNA449855 | ENA

A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation

Project description:Mammalian SWI/SNF chromatin remodeling complexes exist in three distinct, final-form assemblies: canonical BAF (cBAF), PBAF, and a newly characterized non-canonical complex, ncBAF. However, their complex-specific targeting on chromatin, functions and roles in disease remain largely unknown. Here, we comprehensively map complex assemblies on chromatin and find that ncBAF uniquely localizes to CTCF sites and promoters. We identified ncBAF subunits as major synthetic lethalities specific to human synovial sarcoma and malignant rhabdoid tumor, which share in common cBAF complex perturbation. Chemical and biological depletion of the BRD9 subunit of ncBAF rapidly attenuates SS and MRT cell proliferation. Notably, in cBAF-perturbed cancers, ncBAF complexes retain localization to CTCF sites and promoters, and maintain gene expression at retained mSWI/SNF sites to support cell proliferation in a manner distinct from fusion oncoprotein-mediated targeting. Taken together, these findings unmask the unique targeting and function of ncBAF complexes and present new cancer-specific therapeutic targets.

2018-11-06 | PXD011103 | Pride

A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation [RNA-seq]

Project description:Mammalian SWI/SNF chromatin remodeling complexes exist in three distinct, final-form assemblies: canonical BAF (cBAF), PBAF, and a newly characterized non-canonical complex, ncBAF. However, their complex-specific targeting on chromatin, functions and roles in disease remain largely unknown. Here, we comprehensively map complex assemblies on chromatin and find that ncBAF uniquely localizes to CTCF sites and promoters. We identified ncBAF subunits as major synthetic lethalities specific to human synovial sarcoma and malignant rhabdoid tumor, which share in common cBAF complex perturbation. Chemical degradation of the BRD9 subunit of ncBAF rapidly attenuates SS and MRT cell proliferation. Notably, in cBAF-perturbed cancers, ncBAF complexes retain their hallmark localization to CTCF sites and promoters, and maintain gene expression at retained mSWI/SNF sites to support cell proliferation in a manner distinct from fusion oncoprotein-mediated targeting. Taken together, these findings unmask the unique targeting and function of ncBAF complexes and present new cancer-specific therapeutic targets.

2018-11-04 | GSE113041 | GEO

A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation [ChIP-seq]

Project description:Mammalian SWI/SNF chromatin remodeling complexes exist in three distinct, final-form assemblies: canonical BAF (cBAF), PBAF, and a newly characterized non-canonical complex, ncBAF. However, their complex-specific targeting on chromatin, functions and roles in disease remain largely unknown. Here, we comprehensively map complex assemblies on chromatin and find that ncBAF uniquely localizes to CTCF sites and promoters. We identified ncBAF subunits as major synthetic lethalities specific to human synovial sarcoma and malignant rhabdoid tumor, which share in common cBAF complex perturbation. Chemical degradation of the BRD9 subunit of ncBAF rapidly attenuates SS and MRT cell proliferation. Notably, in cBAF-perturbed cancers, ncBAF complexes retain their hallmark localization to CTCF sites and promoters, and maintain gene expression at retained mSWI/SNF sites to support cell proliferation in a manner distinct from fusion oncoprotein-mediated targeting. Taken together, these findings unmask the unique targeting and function of ncBAF complexes and present new cancer-specific therapeutic targets.

2018-11-04 | GSE113040 | GEO

A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-11-04 | GSE113042 | GEO

Acute BAF perturbation causes immediate changes in chromatin accessibility

Project description:Loss-of-function mutations in genes coding for subunits of the large, multifarious BRG1/BRM associated factor (BAF) chromatin remodeling complexes are frequently causative for cancer or developmental diseases1-5. Cells lacking the most frequently mutated subunits like the ATPase SMARCA4 typically exhibit drastic chromatin accessibility changes, especially of important regulatory regions6-12. However, so far it remains unknown how these changes are established over time, and whether they are causative for intra-complex synthetic lethalities abrogating the formation (SMARCC1-SMARCC2)8,13,14 or activity (SMARCA4-SMARCA2)15-17 of BAF complexes. Here, we utilize the dTAG system18 to induce acute degradation of BAF subunits in wild-type and BAF mutant backgrounds and analyze the resulting chromatin accessibility changes with high kinetic resolution. We observe that chromatin alterations are established faster than the duration of one cell cycle and that maintaining genome accessibility requires constant ATP-dependent remodeling. Completely abolishing BAF complex function by acute degradation of a synthetic lethal subunit in a paralog-deficient background results in a near-complete loss of chromatin accessibility at BAF-controlled sites, especially at super-enhancers, providing a mechanism for intra-complex synthetic lethalities.

2020-12-23 | PXD018381 | Pride

Acute BAF perturbation causes immediate changes in chromatin accessibility

Project description:Loss-of-function mutations in genes coding for subunits of the large, multifarious BRG1/BRM associated factor (BAF) chromatin remodeling complexes are frequently causative for cancer or developmental diseases. Cells lacking the most frequently mutated subunits, like the ATPase SMARCA4, typically exhibit drastic chromatin accessibility changes, especially of important regulatory regions. However, so far it remains unknown how these changes are established over time, and whether they are causative for intra-complex synthetic lethalities abrogating the formation or activity of BAF complexes. Here, we utilize the dTAG system to induce acute degradation of BAF subunits in wildtype and BAF mutant backgrounds and analyze the resulting chromatin accessibility changes with high kinetic resolution. We observe that chromatin alterations are established faster than the duration of one cell cycle and that maintaining genome accessibility requires constant ATP-dependent remodeling. Completely abolishing BAF complex function by acute degradation of a synthetic lethal subunit in a paralog-deficient background results in a near-complete loss of chromatin accessibility at BAF-controlled sites, especially at super-enhancers, providing a mechanism for intra-complex synthetic lethalities.

2020-12-22 | GSE148175 | GEO

Acute BAF perturbation causes immediate changes in chromatin accessibility

Project description:Acute BAF perturbation causes immediate changes in chromatin accessibility

| PRJNA623383 | ENA

The BAF chromatin remodeling complex regulates gene expression programs essential for mammalian neural crest development

Project description:Neural crest cells (NCCs) are a multipotent cell population that contributes to the development of many tissues including craniofacial, pharyngeal arch arteries, and cardiac outflow tract (OFT). The BAF complex plays an important role in the development of a wide range of tissues by modulating gene expression programs at the chromatin level. However, its role in neural crest development has remained unclear. To determine the role BAF complex, we deleted BAF155 and BAF170, the core subunits required for the assembly, stability, and functions of the BAF complex in NCCs. Mouse embryos lacking BAF155/170 in NCCs displayed early lethality due to a wide range of developmental defects including craniofacial defects, pharyngeal arch artery defects, and OFT defects. We observed reduced proliferation, increased cell death, and impaired migration of cardiac NCCs to the OFT in BAF155/170 mutants. RNAseq analysis on sorted NCCs revealed that the BAF complex regulates the expression of numerous genes essential for neural crest development. We observed downregulation of Hippo and Notch signaling pathways, both essential for the migration, proliferation, and differentiation of the NCCs. The BAF complex interacts with transcription factors to modulate the transcriptional program. Therefore, we performed transcription factor enrichment analysis on the RNAseq data set and identified several transcription factors including Hey1, Hey2, and Hes5 that may directly or indirectly interact with the BAF complex in NCCs. We also found that Brg1 interact with Tead transcription factors and the interaction was impaired in BAF155/170 knockdown cells. Together, our results demonstrate an important role of the BAF complex in modulating the gene regulatory network essential for neural crest development.

2021-03-05 | GSE153121 | GEO

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