Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PBRM1 bromodomains associate with RNA to facilitate chromatin association (ChIP-seq)

ABSTRACT: PBRM1 is a subunit of the PBAF chromatin remodeling complex, which is mutated in 40-50% of clear cell renal cell carcinoma patients. It is thought to largely function as a chromatin binding subunit of the PBAF complex, but the molecular mechanism underlying this activity is not fully known. PBRM1 contains six tandem bromodomains which are known to cooperate in binding of nucleosomes acetylated at histone H3 lysine 14 (H3K14ac). Using H3K14Ac and PHF10 ChIP-seq, along with CLIP-seq in Caki2 renal cancer cells, we demonstrate here that the second and fourth bromodomains from PBRM1 also bind nucleic acids, selectively associating with double stranded RNA elements. Disruption of the RNA binding pocket is found to compromise PBRM1 chromatin binding and inhibit PBRM1-mediated cellular growth effects.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221618 | GEO | 2023/02/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

PBRM1 bromodomains associate with RNA to facilitate chromatin association (CLIP-seq)

Project description:PBRM1 is a subunit of the PBAF chromatin remodeling complex, which is mutated in 40-50% of clear cell renal cell carcinoma patients. It is thought to largely function as a chromatin binding subunit of the PBAF complex, but the molecular mechanism underlying this activity is not fully known. PBRM1 contains six tandem bromodomains which are known to cooperate in binding of nucleosomes acetylated at histone H3 lysine 14 (H3K14ac). Using H3K14Ac and PHF10 ChIP-seq, along with CLIP-seq in Caki2 renal cancer cells, we demonstrate here that the second and fourth bromodomains from PBRM1 also bind nucleic acids, selectively associating with double stranded RNA elements. Disruption of the RNA binding pocket is found to compromise PBRM1 chromatin binding and inhibit PBRM1-mediated cellular growth effects.

2023-02-24 | GSE221619 | GEO

Transcriptome profiling of Caki2 cells re-expressing Polybromo-1 (PBRM1)

Project description:PBRM1 is a component of the PBAF chromatin remodelling complex and has been observed to be deregulated in a significant proportion of patients with clear-cell Renal Cell Carcinoma (ccRCC). This study employs RNA-Seq to identify differentially expressed genes in cellular models of ccRCC by expressing PBRM1 in PBRM1-deficient Caki2 cells.

2016-05-04 | GSE76199 | GEO

PBRM1-deficient PBAF complexes target de novo genomic loci to activate pro-survival genes in clear cell renal cell carcinoma (BRG1 dataset)

Project description:PBRM1 is lost in 40% of clear cell renal cell carcinomas (ccRCC) and the combined loss of VHL and PBRM1 drives ccRCC tumorigenesis. PBRM1 is an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and despite its well-established role as a tumor suppressor, we have limited understanding of how PBRM1 regulates the chromatin. Now we report that PBRM1 binds to promoter-proxy regions with footprints at +1 to + 3 nucleosomes. PBRM1-deficient PBAF complexes lose BRD7 but retain ARID2, while tethered to SMARCA4. The lack of PBRM1-BRD7 module compromises the targeting specificity of the PBAF complexes, causes their genomic redistribution and impairs the repressive ability of PBAF complexes. Subsequently, PBRM1-deficient PBAF complexes prime the chromatin at de novo sites for transcriptional activation of pro-survival genes involved in hypoxia and cholesterol synthesis. Therefore, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-survival genes by residual PBRM1-deficient SWI/SNF complexes.

2021-07-24 | PXD020553 | JPOST Repository

PBRM1-deficient PBAF complexes target de novo genomic loci to activate pro-survival genes in clear cell renal cell carcinoma (PBRM1 dataset)

2021-07-24 | PXD020554 | JPOST Repository

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

Genome-wide chromatin profiles of PBRM1 [RNA-Seq]

Project description:PBRM1 is an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler. The inactivation of PBRM1 is the second most frequent mutational event in kidney tumorigenesis. Here we show that in VHL-deficient ccRCC tumors, PBRM1 loss results in an altered PBAF complex that retains the association between SMARCA4 and ARID2 but disengages BRD7 from SMARCA4. The PBRM1-deficient PBAF complexes redistribute from promoter proxy regions to distal enhancer regions. The ATPase function of SMARCA4 enhances the recruitment of nuclear factor RELA to aberrant sites and promotes NF-κB activity. Proteasome inhibitor bortezomib reverses NF-κB activation by reducing RELA binding at regions bound by PBRM1-deficient PBAF and delays PBRM1-deficient tumor growth. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes.

2023-02-13 | GSE152734 | GEO

Genome-wide chromatin profiles of PBRM1 Drug treatment [RNA-Seq]

Project description:PBRM1 encodes an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and the inactivation of PBRM1 is the second most frequent mutational event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodeling, especially pertaining to kidney tumorigenesis, has not been well examined. Here we show that in VHL-deficient renal tumors, PBRM1 deficiency results in aberrant PBAF complexes that localize to de novo genomic loci and activate the pro-tumorigenic NF-κB pathway. PBRM1-deficient PBAF complexes, despite retaining the association between SMARCA4 and ARID2, have loosely tethered BRD7 and redistribute from promoter proximal regions to distal enhancers containing NF-κB motifs. Subsequently, PBRM1-deficient cells display heightened NF-κB activity in multiple models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of both pre-existing and newly acquired RELA specific to PBRM1 loss, and activates downstream target gene expression. Proteasome inhibitor bortezomib reverses NF-κB activation by reducing RELA occupancy and delays growth of PBRM1-deficient tumors. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes.

2023-02-13 | GSE222245 | GEO

Genome-wide chromatin profiles of PBRM1 Drug treatment [ChIP-Seq]

2023-02-13 | GSE222244 | GEO

Genome-wide chromatin profiles of PBRM1 [ChIP-Seq]

Project description:PBRM1 encodes an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and the inactivation of PBRM1 is the second most frequent mutational event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodeling, especially pertaining to kidney tumorigenesis, has not been well examined. Here we show that in VHL-deficient renal tumors, PBRM1 deficiency results in aberrant PBAF complexes that localize to de novo genomic loci and activate the pro-tumorigenic NF-?B pathway. PBRM1-deficient PBAF complexes, despite retaining the association between SMARCA4 and ARID2, have loosely tethered BRD7 and redistribute from promoter proximal regions to distal enhancers containing NF-?B motifs. Subsequently, PBRM1-deficient cells display heightened NF-?B activity in multiple models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of both pre-existing and newly acquired RELA specific to PBRM1 loss, and activates downstream target gene expression. Proteasome inhibitor bortezomib reverses NF-?B activation by reducing RELA occupancy and delays growth of PBRM1-deficient tumors. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-?B target genes by residual PBRM1-deficient PBAF complexes.

2023-02-13 | GSE152681 | GEO

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data