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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. 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.

Pubmed ID: 22169041

Authors

  • Jiang XX
  • Nguyen Q
  • Chou Y
  • Wang T
  • Nandakumar V
  • Yates P
  • Jones L
  • Wang L
  • Won H
  • Lee HR
  • Jung JU
  • Müschen M
  • Huang XF
  • Chen SY

Journal

Immunity

Publication Data

December 23, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI068472
  • Agency: NIAID NIH HHS, Id: AI073099
  • Agency: NIAID NIH HHS, Id: AI08185
  • Agency: NIAID NIH HHS, Id: AI083025
  • Agency: NIAID NIH HHS, Id: AI084811
  • Agency: NCI NIH HHS, Id: CA100841
  • Agency: NCI NIH HHS, Id: CA115284
  • Agency: NCI NIH HHS, Id: CA116677
  • Agency: NCI NIH HHS, Id: CA31363
  • Agency: NCI NIH HHS, Id: CA82057
  • Agency: NCI NIH HHS, Id: R01 CA031363
  • Agency: NCI NIH HHS, Id: R01 CA115284
  • Agency: NCI NIH HHS, Id: R01 CA115284-06A1
  • Agency: NCI NIH HHS, Id: R01CA090427

Mesh Terms

  • Animals
  • B-Lymphocytes
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Cell Lineage
  • Chromosomal Proteins, Non-Histone
  • Endopeptidases
  • Gene Expression Regulation
  • Histones
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Protein Binding
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic