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Series GSE222244 Query DataSets for GSE222244
Status Public on Feb 13, 2023
Title Genome-wide chromatin profiles of PBRM1 Drug treatment [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design ChIP-seq of parental and PBRM1-deficient 786-O cells treated with SMARCA4 ATPase inhibitor BRM014 and bortezomib
 
Contributor(s) Yao X, Teh BT
Citation(s) 37095322
Submission date Jan 05, 2023
Last update date May 15, 2023
Contact name Xiaosai Yao
E-mail(s) xiaosai.yao@gmail.com, yao.xiaosai@gene.com
Phone +65 68088271
Organization name Genome Institute of Singapore
Street address 60 Biopolis Street, Genome, #02-01
City Singapore
ZIP/Postal code 138672
Country Singapore
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (32)
GSM6918819 RELA_786O_PBRM1WT_DMSO_9hr_ChIPSeq_rep1
GSM6918820 RELA_786O_PBRM1WT_BTZ_9hr_ChIPSeq_rep1
GSM6918821 RELA_786O_PBRM1KO_DMSO_9hr_ChIPSeq_rep1
This SubSeries is part of SuperSeries:
GSE152735 Genome-wide chromatin profiles of PBRM1
Relations
BioProject PRJNA918665

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE222244_RAW.tar 59.7 Mb (http)(custom) TAR (of NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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