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PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (Chromatin)

ABSTRACT: PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (Chromatin)

PROVIDER: PRJNA723190 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14279724.fastq.gz	Fastqsanger.gz
	SRR14279725.fastq.gz	Fastqsanger.gz
	SRR14279726.fastq.gz	Fastqsanger.gz
	SRR14279728.fastq.gz	Fastqsanger.gz
	SRR14279730.fastq.gz	Fastqsanger.gz

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PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics

Project description:PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics

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PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (RNA-Seq)

Project description:PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (RNA-Seq)

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PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (Chromatin)

Project description:ARID2 is an essential subunit of the SWI/SNF PBAF chromatin remodeler and is highly mutate in melanoma. To elucidate the role of ARID2 in melanoma biology and chromatin structure we utilized CRISPR Cas9 methodology to generate isogenic ARID2 WT and KO melanoma clonal cell lines. We further map the genomic localization of several SWI/SNF subunits, open and repressed chromatin markers, and multiple transcription factors to characterize how loss of the PBAF subcomplex alters chromatin accessibility and the melanoma transcription factor network. Finally, we characterized the transcriptional changes produced by PBAF depletion.

2022-04-05 | GSE172383 | GEO

PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics (RNA-Seq)

2022-04-05 | GSE172384 | GEO

PBAF complex deficiency in melanoma mediates BAF occupancy and transcription factor dynamics

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

2022-04-05 | GSE172386 | GEO

Structure of nucleosome-bound human PBAF complex

Project description:BAF and PBAF are mammalian SWI/SNF family chromatin remodeling complexes that possess multiple histone/DNA-binding subunits and create nucleosome-depleted/free regions for transcription activation. Despite previous structural studies and recent advance of SWI/SNF family complexes, it remains incompletely understood how PBAF-nucleosome complex is organized. Here we determined structure of 13-subunit human PBAF in complex with acetylated nucleosome in ADP-BeF3-bound state. Four PBAF-specific subunits work together with nine BAF/PBAF-shared subunits to generate PBAF-specific modular organization, distinct from that of BAF at various regions. PBAF-nucleosome structure reveals six histone-binding domains and four DNA-binding domains/modules, the majority of which directly bind histone/DNA. This multivalent nucleosome-binding pattern, not observed in previous studies, suggests that PBAF may integrate comprehensive chromatin information to target genomic loci for function. Our study reveals molecular organization of subunits and histone/DNA-binding domains/modules in PBAF-nucleosome complex and provides structural insights into PBAF-mediated nucleosome association complimentary to the recently reported PBAF-nucleosome structure.

2023-03-11 | PXD036708 | Pride

PBAF associates with repressed chromatin to enable REST occupancy (RNA-Seq)

Project description:Multimeric SWI/SNF chromatin remodelers assemble in distinct conformations, with individual functions difficult to dissect. Importantly, mutations in specific SWI/SNF genes are enriched in distinct cancers, as the PBAF-specific component ARID2 in melanoma. Through comprehensive epigenomic profiling of SWI/SNF complexes and their associated chromatin states in melanoma and melanocytes, we found that a subset of PBAF-exclusive regions unexpectedly coexists with PRC2 and repressed chromatin. Time-resolved approaches revealed that PBAF regions are generally less sensitive to ATPase-mediated remodeling compared to BAF sites. Notably, PBAF/PRC2-bound loci are enriched for REST, a transcription factor that represses neuronal genes. In turn, absence of ARID2 and consequent PBAF loss hinders REST ability to bind and inactivate its targets, leading to upregulation of neuronal and synaptic transcripts, a gene signature also associated with ARID2 mutations in melanoma patients. In sum, we demonstrate a unique role for PBAF in generating accessibility for a silencing transcription factor at repressed chromatin.

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PBAF associates with repressed chromatin to enable REST occupancy (ChIP-seq)

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PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

Project description:PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

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PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

Project description:The PBAF complex, a member of SWI/SNF family of chromatin remodelers, plays an essential role in transcriptional regulation. We revealed a disease progression associated elevation of PHF10 subunit of PBAF in clinical samples of melanoma. We demonstrated that in melanoma cell lines, PHF10 interacts with MYC and facilitates the recruitment of PBAF complex to target gene promoters, therefore augmenting MYC transcriptional activation of genes involved in the cell cycle progression. Depletion of either PHF10 or MYC induced G1 accumulation and a senescence-like phenotype. Our data identify PHF10 as a pro-oncogenic mechanism and an essential novel link between chromatin remodeling and MYC-dependent gene transcription.

2021-04-08 | GSE164726 | GEO

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