Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1

Frontiers in Immunology

卷:12

Simon Clare¹  Javier M. Di Noia³  Poorani Ganesh Subramani⁵  Anastasia Nijnik⁷  Yue Liang⁹  Yun Hsiao Lin⁹  Michael Förster⁹  Lin Tze Tung⁹  HanChen Wang¹⁰  David Langlais¹⁰ 

[1] Molecular Medicine, Université de Montréal, Montreal, QC, Canada;

[2] 0Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada;

[3] Department of Biochemistry &

[4] Department of Human Genetics, McGill University, Montreal, QC, Canada;

[5] Department of Medicine, McGill University, Montreal, QC, Canada;

[6] Department of Medicine, Université de Montréal, Montreal, QC, Canada;

[7] Department of Physiology, McGill University, Montreal, QC, Canada;

[8] Institut de Recherches Cliniques de Montréal, Montreal, QC, Canada;

[9] McGill Research Centre on Complex Traits, McGill University, Montreal, QC, Canada;

[10] McGill University Genome Centre, Montreal, QC, Canada;

[11] Wellcome Trust Sanger Institute, Hinxton, United Kingdom;

关键词: B cells;    B cell development;    transcriptional regulation;    epigenetic regulation;    mouse models;   

DOI  :  10.3389/fimmu.2021.626418

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown