title: Control of B cell development by the histone H2A deubiquitinase MYSM1.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Jiang
authors.forename: Quan
authors.initials: Q
authors.lastname: Nguyen
authors.forename: YuChia
authors.initials: Y
authors.lastname: Chou
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Nandakumar
authors.forename: Peter
authors.initials: P
authors.lastname: Yates
authors.forename: Lindsey
authors.initials: L
authors.lastname: Jones
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.forename: Haejung
authors.initials: H
authors.lastname: Won
authors.forename: Hye-Ra
authors.initials: HR
authors.lastname: Lee
authors.forename: Jae U
authors.initials: JU
authors.lastname: Jung
authors.forename: Markus
authors.initials: M
authors.lastname: Müschen
authors.forename: Xue F
authors.initials: XF
authors.lastname: Huang
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D064570:Ubiquitin-Specific Proteases
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002868:Chromosomal Proteins, Non-Histone; D010450:Endopeptidases; D006657:Histones; D015534:Trans-Activators; D014157:Transcription Factors; D064570:Ubiquitin-Specific Proteases; C489921:Ebf1 protein, mouse; C445179:SWI-SNF-B chromatin-remodeling complex; C075668:Tcf3 protein, mouse; C570173:MYSM1 protein, mouse