B-cell Intrinsic Regulation of Antibody Mediated Immunity by Histone H2A Deubiquitinase BAP1 [ChIP-seq]
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PROVIDER: PRJNA1027438 | ENA |
REPOSITORIES: ENA
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Project description:BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. In the current study, we demonstrate that a B-cell intrinsic loss of BAP1 function in activated B cells in the Bap1fl/fl Cγ1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. In summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity.
2024-02-15 | GSE245220 | GEO
Project description:BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. In the current study, we demonstrate that a B-cell intrinsic loss of BAP1 function in activated B cells in the Bap1fl/fl Cγ1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. In summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity.
2024-02-15 | GSE244623 | GEO
Project description:B-cell Intrinsic Regulation of Antibody Mediated Immunity by Histone H2A Deubiquitinase BAP1 [RNA-seq]
| PRJNA1023907 | ENA
Project description:The goal of the experiment was to determine the role of H2A deubiquitinase in the nerve injury response in peripheral nerve. A Schwann cell specific knockout of the H2A deubiquitinase (Bap1) was generated to compare with wild type mice.
2022-05-02 | GSE197149 | GEO
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
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 | GSE162084 | GEO
Project description:Regulation of B lymphocyte development by histone H2A deubiquitinase BAP1
| PRJNA680531 | ENA
Project description:Regulation of B lymphocyte development by histone H2A deubiquitinase BAP1 (BAP1_ChIP-Seq)
| PRJNA680532 | ENA
Project description:Regulation of B lymphocyte development by histone H2A deubiquitinase BAP1 (Bap1KO_RNA-Seq)
| PRJNA680533 | ENA
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