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Series GSE162739 Query DataSets for GSE162739
Status Public on Jun 27, 2021
Title BAP1 activity regulates Polycomb occupancy and global chromatin condensation counteracting diffuse PCGF3/5-dependent H2AK119ub1 deposition
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary BAP1 is recurrently mutated or deleted in a large number of diverse cancer types, including mesothelioma, uveal melanoma and hepatocellular cholangiocarcinoma. BAP1 is the catalytic subunit of the Polycomb Repressive De-Ubiquitination complex (PR-DUB) which removes PRC1 mediated H2AK119ub1. We and others have shown that H2AK119ub1 is essential for maintaining transcriptional repression and contributes to PRC2 chromatin recruitment. However, the precise relationship between BAP1 and PRC1 remains mechanistically elusive. Using embryonic stem cells, we show that a major function of BAP1 is to restrict H2AK119ub1 deposition to target sites. This increases the stability of PcG complexes with their targets and prevents diffuse accumulation of H2AK119ub1 and H3K27me3 modifications. Loss of BAP1 results in a broad increase in H2AK119ub1 levels that are primarily dependent on PCGF3/5-PRC1 complexes with a mechanism that is reminiscent of X-chromosome inactivation. Increased genome-wide H2AK119ub1 levels titrates away PRC2 from its targets and stimulates diffuse H3K27me3 accumulation across the genome. This decreases the activity of PcG repressive machineries at physiological targets and induces a general compaction of the entire chromatin. Our findings provide evidences for a unifying model that resolves the apparent contradiction between BAP1 catalytic activity and its role in vivo, uncovering molecular vulnerabilities that could be useful for BAP1-related pathologies.
Overall design Profiling of histone modification and gene expression in mouse embryonic stem cells in wild-type and BAP1-KO. Characterisation of chromatin conformation structure by HiC.
Contributor(s) Conway E, Rossi F, Tamburri S, Ponzo E, Ferrari KJ, Zanotti M, Fernandez-Perez D, Manganaro D, Rodighiero S, Pasini D
Citation(s) 34186021
Submission date Dec 06, 2020
Last update date Sep 22, 2021
Contact name Federico Rossi
Organization name Istituto Europeo Oncologia
Street address Via Adamello 16
City Milan
ZIP/Postal code 10142
Country Italy
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (192)
GSM4958798 E14-input
GSM4958799 WT-input.1
GSM4958800 BAP1-KO-clone1-input.1
BioProject PRJNA682824
SRA SRP296576

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
GSE162739_Bap1KO-C91S-vs-Bap1KO-WT_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 779.0 Kb (ftp)(http) TSV
GSE162739_Bap1KO-C91S-vs-PAR_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 712.4 Kb (ftp)(http) TSV
GSE162739_Bap1KO-WT-vs-PAR_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 773.5 Kb (ftp)(http) TSV
GSE162739_Bap1KO_C91S_DMSO-vs-WT_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 740.2 Kb (ftp)(http) TSV
GSE162739_Bap1KO_C91S_DMSO-vs-WT_EV_RA_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 799.6 Kb (ftp)(http) TSV
GSE162739_Bap1KO_C91S_RA-vs-Bap1KO_C91S_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 769.0 Kb (ftp)(http) TSV
GSE162739_Bap1KO_C91S_RA-vs-WT_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 779.6 Kb (ftp)(http) TSV
GSE162739_Bap1KO_C91S_RA-vs-WT_EV_RA_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 733.6 Kb (ftp)(http) TSV
GSE162739_Bap1KO_EV_DMSO-vs-WT_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 763.9 Kb (ftp)(http) TSV
GSE162739_Bap1KO_EV_DMSO-vs-WT_EV_RA_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 804.0 Kb (ftp)(http) TSV
GSE162739_Bap1KO_EV_RA-vs-Bap1KO_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 774.4 Kb (ftp)(http) TSV
GSE162739_Bap1KO_EV_RA-vs-WT_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 785.5 Kb (ftp)(http) TSV
GSE162739_Bap1KO_EV_RA-vs-WT_EV_RA_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 745.5 Kb (ftp)(http) TSV
GSE162739_Bap1KO_WT_DMSO-vs-WT_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 670.7 Kb (ftp)(http) TSV
GSE162739_Bap1KO_WT_DMSO-vs-WT_EV_RA_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 780.0 Kb (ftp)(http) TSV
GSE162739_Bap1KO_WT_RA-vs-Bap1KO_WT_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 757.2 Kb (ftp)(http) TSV
GSE162739_Bap1KO_WT_RA-vs-WT_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 758.6 Kb (ftp)(http) TSV
GSE162739_Bap1KO_WT_RA-vs-WT_EV_RA_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 647.0 Kb (ftp)(http) TSV
GSE162739_RAW.tar 7.5 Gb (http)(custom) TAR (of BED, RPKM, TSV, TXT)
GSE162739_Raw_counts.tsv.gz 1.0 Mb (ftp)(http) TSV
GSE162739_WT_EV_DMSO-vs-WT_EV_RA_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 771.4 Kb (ftp)(http) TSV
GSE162739_WT_EV_RA-vs-WT_EV_DMSO_diffexp_log2fc1_pval0.05_fpkm0.tsv.gz 770.1 Kb (ftp)(http) TSV
GSE162739_counts.tsv.gz 563.4 Kb (ftp)(http) TSV
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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