Expression profiles of restoration of BAP1 in a BAP1 deficient cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE97224 | GEO | 2018/01/31
REPOSITORIES: GEO
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Project description:Transcriptome analysis of BAP1 knockout and restoration
| PRJNA381014 | ENA
Project description:We report the genome wide binding sites of BAP1, HCF1 and OGT in bone marrow derived macrophages. De-ubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with increased risk of mesothelioma and uveal melanoma. Somatic BAP1 mutations occur in various malignancies. We show that mouse Bap1 gene deletion is lethal during embryogenesis, but systemic or hematopoietic-restricted deletion in adults recapitulates features of human myelodysplastic syndrome (MDS). Knockin mice expressing BAP1 with a 3xFlag tag revealed that BAP1 interacts with host cell factor–1 (HCF-1), O-linked N-acetylglucosamine transferase (OGT), and the polycomb group proteins ASXL1 and ASXL2 in vivo. OGT and HCF-1 levels were decreased by Bap1 deletion, indicating a critical role for BAP1 in stabilizing these epigenetic regulators. Human ASXL1 is mutated frequently in chronic myelomonocytic leukemia (CMML) so an ASXL/BAP1 complex may suppress CMML. A BAP1 catalytic mutation found in a MDS patient implies that BAP1 loss of function has similar consequences in mice and humans. For BAP1, bone marrow derived macrophages were used differentiated from bone marrow cells of BAP1-3X Flag Tagged KI mice we generated. For OGT and HCF1, bone marrow derived macrophages were used from BAP1 WT mice.
2012-11-07 | E-GEOD-40723 | biostudies-arrayexpress
Project description:BAP1 has been studied as a tumor suppressor. Our aim was to characterize genes that were altered in various hematopoietic cell types upon deletion of BAP1. BAP1 WT versus KO cells.
2012-11-07 | E-GEOD-40541 | biostudies-arrayexpress
Project description:Malignancies arising from mutation of tumor suppressor genes display an unexplained tissue proclivity. For example, tumor suppressor BAP1 encodes a ubiquitously expressed deubiquitinase for histone H2A but germline mutations predominantly cause uveal melanomas and mesotheliomas. We show that BAP1 inactivation causes apoptosis in mouse embryonic stem cells, fibroblasts, liver and pancreas, whereas melanocytes and mesothelial cells remain viable. E3 ligase RNF2, which silences genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing the pro-survival genes Bcl-2 and Mcl-1. Our data argue that BAP1 modulates gene expression by countering H2A ubiquitination, but its loss only promotes tumorigenesis in cells that do not engage an RNF2-dependent apoptotic program. We propose that intolerance of BAP1 loss, and perhaps the loss of other tumor suppressors, restricts the mutant tumor spectrum.
2019-03-26 | GSE120413 | GEO
Project description:We report the genome wide binding sites of BAP1, HCF1 and OGT in bone marrow derived macrophages. De-ubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with increased risk of mesothelioma and uveal melanoma. Somatic BAP1 mutations occur in various malignancies. We show that mouse Bap1 gene deletion is lethal during embryogenesis, but systemic or hematopoietic-restricted deletion in adults recapitulates features of human myelodysplastic syndrome (MDS). Knockin mice expressing BAP1 with a 3xFlag tag revealed that BAP1 interacts with host cell factor–1 (HCF-1), O-linked N-acetylglucosamine transferase (OGT), and the polycomb group proteins ASXL1 and ASXL2 in vivo. OGT and HCF-1 levels were decreased by Bap1 deletion, indicating a critical role for BAP1 in stabilizing these epigenetic regulators. Human ASXL1 is mutated frequently in chronic myelomonocytic leukemia (CMML) so an ASXL/BAP1 complex may suppress CMML. A BAP1 catalytic mutation found in a MDS patient implies that BAP1 loss of function has similar consequences in mice and humans.
2012-11-07 | GSE40723 | GEO
Project description:More than half of malignant mesothelioma patients show alterations in the BAP1 tumour suppressor gene. Being a member of the Polycomb repressive deubiquitinating (PR-DUB) complex, BAP1 loss results in an altered epigenome which may create new vulnerabilities that remain largely unknown. Here we performed a CRISPR/Cas9-kinome screen in mesothelioma cells that identified two kinases in the Mevalonate/Cholesterol biosynthesis pathway. Furthermore, our analysis of chromatin, expression and genetic perturbation data in mesothelioma cells suggests a dependency on Polycomb repressive complex 2 (PRC2) mediated silencing. Pharmacological inhibition of PRC2 elevates the expression of cholesterol biosynthesis genes only in BAP1-deficient mesothelioma, thereby sensitizing these cells to the combined targeting of PRC2 and the mevalonate pathway. Finally, by subjecting autochthonous Bap1-deficient mesothelioma mice or xenografts to mevalonate pathway inhibition (Zoledronic Acid) and PRC2 inhibition (Tazemetostat), we demonstrate a potent anti-tumour effect, suggesting a targeted combination therapy for Bap1-deficient mesothelioma
2023-01-12 | GSE222376 | GEO
Project description:The deubiquitinase BAP1 is a candidate tumor suppressor regulating cell proliferation in human and is required for development in Drosophila. BAP1 is assembled into high molecular weight transcriptional multi-protein complexes. In order to identify potential BAP1 target genes, global mRNA expression profiling using microarrays was conducted. U2OS cells, transfected with a non-target control shRNA or shRNAs targeting BAP1, were selected with puromycin containing medium and then synchronized at the G1/S border to allow comparative analysis of gene expression.
2010-11-05 | E-GEOD-23035 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice retained >92% of mutations and exhibited similar DNA copy number alterations to corresponding primary tumors. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. The genomic DNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal samples were labeled and hybridized to Affymetrix SNP arrays 6.0.
2012-06-09 | E-GEOD-25540 | biostudies-arrayexpress
Project description:BAP1 deletion in primary mouse epidermal cell culture leads to increased melanocytes population. However, it is unclear whether BAP1 exhibits its function in melanocytes or in the progenitor cells for melanocytes, since the epidermal culture contains a mixed cell types. We aim to carry out a single cell RNAseq profiling with this system, and dissect BAP1's roles in different cell types.
2019-03-26 | GSE120421 | GEO
Project description:Malignancies arising from mutation of tumor suppressor genes display an unexplained tissue proclivity. For example, tumor suppressor BAP1 encodes a ubiquitously expressed deubiquitinase for histone H2A but germline mutations predominantly cause uveal melanomas and mesotheliomas. We show that BAP1 inactivation causes apoptosis in mouse embryonic stem cells, fibroblasts, liver and pancreas, whereas melanocytes and mesothelial cells remain viable. E3 ligase RNF2, which silences genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing the pro-survival genes Bcl-2 and Mcl-1. Our data argue that BAP1 modulates gene expression by countering H2A ubiquitination, but its loss only promotes tumorigenesis in cells that do not engage an RNF2-dependent apoptotic program. We propose that intolerance of BAP1 loss, and perhaps the loss of other tumor suppressors, restricts the mutant tumor spectrum.
2019-03-26 | GSE120414 | GEO