Control of B Cell Development by the Histone H2A Deubiquitinase MYSM1

• 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
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2011.11.010

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