Control of B Cell Development by the Histone H2A Deubiquitinase MYSM1

Epigenetic histone modifications play critical roles in the control of gene transcription. Recently, an increasing number of histone H2A deubiquitinases have been identified and characterized. However, the physiological functions for this entire group of histone H2A deubiquitinases remain unknown. I...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2011-12, Vol.35 (6), p.883-896
Main Authors: Jiang, Xiao-Xia, Nguyen, Quan, Chou, YuChia, Wang, Tao, Nandakumar, Vijayalakshmi, Yates, Peter, Jones, Lindsey, Wang, Lifeng, Won, Haejung, Lee, Hye-Ra, Jung, Jae U., Müschen, Markus, Huang, Xue F., Chen, Si-Yi
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - cytology
B-Lymphocytes - enzymology
B-Lymphocytes - metabolism
Basic Helix-Loop-Helix Transcription Factors - metabolism
Bone marrow
Cell Differentiation
Cell Lineage - genetics
Chromosomal Proteins, Non-Histone - metabolism
Cloning
Deoxyribonucleic acid
Development
DNA
DNA repair
Endopeptidases - metabolism
Experiments
Flow cytometry
Gene expression
Gene Expression Regulation
Histones - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Plasmids
Promoter Regions, Genetic
Protein Binding
Proteins
Rodents
Trans-Activators - genetics
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic
Yeast
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Summary:Epigenetic histone modifications play critical roles in the control of gene transcription. Recently, an increasing number of histone H2A deubiquitinases have been identified and characterized. However, the physiological functions for this entire group of histone H2A deubiquitinases remain unknown. In this study, we revealed that the histone H2A deubiquitinase MYSM1 plays an essential and intrinsic role in early B cell development. MYSM1 deficiency results in a block in early B cell commitment and a defect of B cell progenitors in expression of EBF1 and other B lymphoid genes. We further demonstrated that MYSM1 derepresses EBF1 transcription in B cell progenitors by orchestrating histone modifications and transcription factor recruitment to the EBF1 locus. Thus, this study not only uncovers the essential role for MYSM1 in gene transcription during early B cell development but also underscores the biological significance of reversible epigenetic histone H2A ubiquitination. [Display omitted] ► The histone H2A deubiquitinase MYSM1 is essential for B cell development ► MYSM1 derepresses EBF1 transcription ► MYSM1 orchestrates histone modifications and transcription factor recruitment
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2011.11.010