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

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

PROVIDER: PRJNA723186 | ENA |

REPOSITORIES: ENA

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

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

| PRJNA723190 | ENA

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)

| PRJNA723192 | ENA

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

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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Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis. [RNA-seq]

Project description:Chromosomal rearrangements resulting in the fusion of TMRPSS2, an androgen-regulated gene, and the ETS family transcription factor ERG occur in over half of prostate cancers. However, the mechanism by which ERG promotes oncogenic gene expression and proliferation remains incompletely understood. Here, we identify a binding interaction between ERG and the mammalian SWI/SNF (BAF) ATP-dependent chromatin remodeling complex, which is conserved among other ETS factors, including ETV1, ETV4, and ETV5. We find that ERG drives genome-wide retargeting of BAF complexes in a manner dependent on binding of ERG to the ETS DNA motif. Moreover, ERG requires intact BAF complexes for chromatin occupancy and BAF complex ATPase activity for target gene regulation. In a prostate organoid model, BAF complexes are required for ERG-mediated basal-to-luminal transition, a hallmark of ERG activity in prostate cancer. These observations suggest a fundamental interdependence between ETS transcription factors and BAF chromatin remodeling complexes in cancer.

2018-08-02 | GSE110656 | GEO

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