Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Disruption of the epigenetic regulator BAP1 drives chromatin remodeling leading to the emergence of cells with breast cancer stem cell properties and aberrant glycosylation [ATACseq_3D]

ABSTRACT: Epigenetic regulator genes are key in controlling cell identity and are frequently disrupted in breast cancers. However, specific epigenetic drivers (epidrivers) of mammary cell plasticity and their mechanistic contributions to this phenotype are poorly characterized. Here, we employed a CRISPR/Cas9 loss-of-function screening strategy to identify potential epidrivers of the emergence of mesenchymal breast cancer stem cell-like phenotypes in non-tumorigenic mammary cells. We unveiled that loss of the histone deubiquitinase BAP1 led to increased expression of breast cancer stem cell and several epithelial-to-mesenchymal transition markers accompanied by disrupted cell organization in mammary spheroids. In-depth characterization of epigenome and transcriptome changes following BAP1 loss revealed less permissive chromatin and downregulation in gene expression impacting programs that control cellular glycosylation, leading to decreased glycan abundance and complexity. BAP1 rescue restored the expression of several deregulated genes in a catalytic activity-dependent manner, suggesting that BAP1-mediated cell identity and glycosylation regulation are dependent on its histone deubiquitinase activity. Our results point to BAP1 as an epidriver of mammary cell plasticity and glycosylation aberrations, through the disruption of its histone modifying and gene expression regulation roles.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271682 | GEO | 2026/01/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Disruption of the epigenetic regulator BAP1 drives chromatin remodeling leading to the emergence of cells with breast cancer stem cell properties and aberrant glycosylation [RNAseq_3D]

Project description:Epigenetic regulator genes are key in controlling cell identity and are frequently disrupted in breast cancers. However, specific epigenetic drivers (epidrivers) of mammary cell plasticity and their mechanistic contributions to this phenotype are poorly characterized. Here, we employed a CRISPR/Cas9 loss-of-function screening strategy to identify potential epidrivers of the emergence of mesenchymal breast cancer stem cell-like phenotypes in non-tumorigenic mammary cells. We unveiled that loss of the histone deubiquitinase BAP1 led to increased expression of breast cancer stem cell and several epithelial-to-mesenchymal transition markers accompanied by disrupted cell organization in mammary spheroids. In-depth characterization of epigenome and transcriptome changes following BAP1 loss revealed less permissive chromatin and downregulation in gene expression impacting programs that control cellular glycosylation, leading to decreased glycan abundance and complexity. BAP1 rescue restored the expression of several deregulated genes in a catalytic activity-dependent manner, suggesting that BAP1-mediated cell identity and glycosylation regulation are dependent on its histone deubiquitinase activity. Our results point to BAP1 as an epidriver of mammary cell plasticity and glycosylation aberrations, through the disruption of its histone modifying and gene expression regulation roles.

2026-01-07 | GSE271681 | GEO

Disruption of the epigenetic regulator BAP1 drives chromatin remodeling leading to the emergence of cells with breast cancer stem cell properties and aberrant glycosylation [gRNA_MiSeq]

2026-01-07 | GSE271684 | GEO

Disruption of the epigenetic regulator BAP1 drives chromatin remodeling leading to the emergence of cells with breast cancer stem cell properties and aberrant glycosylation [ChiPseq_2D]

2026-01-07 | GSE271683 | GEO

Disruption of the epigenetic regulator BAP1 drives chromatin remodeling leading to the emergence of cells with breast cancer stem cell properties and aberrant glycosylation [RNAseq_2D]

2026-01-07 | GSE271680 | GEO

Therapeutic targeting of BAP1/ASXL3 sub-complex in ASCL1-dependent small cell lung cancer

Project description:Small cell lung cancer (SCLC) is an aggressive disease, with patients diagnosed with either early-stage, limited stage, or extensive stage of SCLC tumor progression. Discovering and targeting the functional biomarkers for SCLC will be crucial in understanding the molecular basis underlying SCLC tumorigenesis to better assist in improving clinical treatment. Emerging studies have demonstrated that dysregulations in BAP1 histone H2A deubiquitinase complex are collectively associated with pathogenesis in human SCLC. Here, we investigated the function of the oncogenic BAP1/ASXL3/BRD4 epigenetic axis in SCLC by developing a next-generation BAP1 inhibitor, iBAP-II, and focusing on the epigenetic balance established between BAP1 and non-canonical PRC1 complexes in regulating SCLC-specific transcriptional programming. We further demonstrated that pharmacologic inhibition of BAP1’s catalytic activity dramatically disrupted BAP1/ASXL3/BRD4 epigenetic axis by inducing protein degradation of the ASXL3 scaffold protein, which bridges BRD4 and BAP1 at active enhancers. Furthermore, treatment of iBAP-II dramatically inhibits SCLC cell viability and tumor growth in vivo via repression of neuroendocrine lineage-specific ASCL1/MYCL/E2F signaling in cells.

2022-02-23 | GSE191106 | GEO

Expression data from BAP1 depleted cells

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

Bap1 loss results in EZH2 dependent transformation

Project description:BAP1 and ASXL1 interact to form a polycomb deubiquitinase complex that removes monoubiquitin from histone H2A lysine 119 (H2AK119Ub). However, BAP1 and ASXL1 are mutated in distinct cancer types, consistent with independent roles in regulating epigenetic state and malignant transformation. Here we demonstrate that Bap1 loss results in increased trimethylated histone H3 lysine 27 (H3K27me3), elevated Ezh2 expression, and enhanced repression of Polycomb Repressive Complex 2 (PRC2) targets. These findings contrast with the reduction in H3K27me3 seen with Asxl1 loss. Conditional deletion of Bap1 and Ezh2 in vivo abrogates the myeloid progenitor expansion induced by Bap1 loss alone.

2015-10-05 | GSE61360 | GEO

Regulation of B lymphocyte development by histone H2A deubiquitinase BAP1 (BAP1_ChIP-Seq)

Project description:BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, via deubiquitination of histone H2AK119ub and other substrates. BAP1 is an important tumour suppressor in human, expressed and functional across many cell-types and tissues, including those of the immune system. B lymphocytes are the mediators of humoral immune response, however the role of BAP1 in B cell development and physiology remains poorly understood. Here we characterize a mouse line with a selective deletion of BAP1 within the B cell lineage (Bap1fl/fl mb1-Cre) and establish a cell intrinsic role of BAP1 in the regulation of B cell development. We demonstrate a depletion of large pre-B cells, transitional B cells, and mature B cells in Bap1fl/fl mb1-Cre mice. We characterize broad transcriptional changes in BAP1-deficient pre-B cells, map BAP1 binding across the genome, and analyze the effects of BAP1-loss on histone H2AK119ub levels and distribution. Overall, our work establishes a cell intrinsic role of BAP1 in B lymphocyte development, and suggests its contribution to the regulation of the transcriptional programs of cell cycle progression, via the deubiquitination of histone H2AK119ub.

2021-03-29 | GSE162083 | GEO

Regulation of B lymphocyte development by histone H2A deubiquitinase BAP1 (Bap1KO_RNA-Seq)

2021-03-29 | GSE162084 | GEO

Expression data from BAP1 depleted cells

2010-11-05 | GSE23035 | GEO