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Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lin, Yun Hsiao 
Liang, Yue 
Wang, HanChen 
Tung, Lin Tze 
Förster, Michael 

Abstract

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 tumor 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.

Description

Keywords

B cell development, B cells, epigenetic regulation, mouse models, transcriptional regulation, Animals, B-Lymphocytes, Cell Lineage, Cell Proliferation, Cells, Cultured, Epigenesis, Genetic, Female, Gene Expression Regulation, Developmental, Histones, Lymphocyte Activation, Male, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Precursor Cells, B-Lymphoid, Protein Processing, Post-Translational, Transcription, Genetic, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Ubiquitination, Mice

Journal Title

Front Immunol

Conference Name

Journal ISSN

1664-3224
1664-3224

Volume Title

12

Publisher

Frontiers Media SA