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PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164726 | GEO | 2021/04/08

REPOSITORIES: GEO

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Specific PBAF complex (dcPBAF) containing PHF10 lacking DPF maintains transcription in differentiated neurons

Project description:The PBAF chromatin-remodeling complex is essential for transcription in mammalian cells. We found that PHF10 specific subunit of PBAF lacking C-terminal DPF is expressed in neurons of adult mouse and human brain. We purified the neuronal PBAF of newborn and adult mouse brain using antibodies against PHF10. We found that specific PBAF, designated as dcPBAF, is dominant in mature neurons. dcPBAF is associated with TAF4, TAF5, TAF6, TAF9 subunits of TFIID, does not contain BRD7 and is characterized by the presence of PHF10 isoform lacking N-terminal amino acids and DPF. The dcPBAF binds promoters of actively transcribed housekeeping and neuron specific genes in terminally differentiated neurons of adult mouse. It maintains high transcription level of neuron specific genes in differentiated human neuronal cell. These data indicate some specific features of PBAF mediated chromatin in terminally differentiated mammalian cells.

2022-08-30 | GSE199351 | GEO

PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

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

| PRJNA691744 | 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

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 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

| PRJNA723186 | ENA

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)

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PBRM-1/PBAF-regulated genes in a multipotent progenitor in C. elegans

Project description:The Caenorhabditiselegans somatic gonadal precursors (SGPs) are multipotent progenitors that generate all somatic cells of the adult reproductive system. The two SGPs originate in the mesodermal layer and are born through a division that produces one SGP and one head mesodermal cell (hmc). One hmc terminally differentiates and the other dies by programmed cell death. The PBAF chromatin remodeling complex promotes the multipotent SGP fate. Complete loss of PBAF causes lethality, so we used a combination of Cre/lox recombination and GFP nanobody-directed protein degradation to eliminate PBRM-1, the signature subunit of the PBAF complex, from 83 mesodermal cells, including SGPs, body muscles, and the hmc. We used RNA sequencing to identify genes acting downstream of PBAF in these cells and identified 1955 transcripts that were significantly differentially expressed between pbrm-1(-) and pbrm-1(+) in the mesoderm of L1 larvae.

2023-12-12 | GSE249603 | GEO

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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Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis

Project description:We identified ADIRF-AS1 as a BMAL1-CLOCK regulated circadian lncRNA. Loss of ADIRF-AS1 in U2OS cells altered rhythmicity of clock-controlled genes and expression of genes associated with cell adhesion and the extracellular matrix (ECM) but did not affect neighboring genes in cis. Affinity based enrichment of U2OS ADIRF-AS1-interacting proteins identified all components of the tumor suppressive PBAF (PBRM1/BRG1) complex. Because PBRM1 is a tumor suppressor mutated in 40% of clear cell renal carcinoma (ccRCC) cases, we studied ccRCC 786O cells and also found PBRM1 bound to ADIRF-AS1. Reducing ADIRF-AS1 expression in 786O and A498 ccRCC cells decreased expression of PBAF-suppressed genes, consistent with ADIRF-AS1 acting to antagonize the function of PBAF. Loss of PBRM1, however, rescued PBAF responsive cell cycle genes in ADIRF-AS1 KO 786O ccRCC cells. Importantly, ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant PBRM1 tumors. In this regard, loss of ADIRF-AS1 did not affect in vitro 786O cell growth, but strikingly eliminated in vivo tumorigenesis, which was partially rescued by concurrent loss of PBRM1. This rescue, however, requires Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1 in regulating the ECM. Collectively, our findings suggest that ADIRF-AS1 functions partly to antagonize the tumor suppressive effect of the PBAF complex and behaves as an unforeseen BMAL1-regulated, oncogenic lncRNA.

2022-11-16 | GSE199825 | GEO

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