EZH2 regulates the developmental timing of effectors of the pre-Antigen receptor checkpoints

Jennifer A. Jacobsen, Jennifer Woodard, Malay Mandal, Marcus R. Clark, Elizabeth Thomas Bartom, Mikael Sigvardsson, Barbara L. Kee*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The histone methyltransferase EZH2 is required for B and T cell development; however, the molecular mechanisms underlying this requirement remain elusive. In a murine model of lymphoid-specific EZH2 deficiency we found that EZH2 was required for proper development of adaptive, but not innate, lymphoid cells. In adaptive lymphoid cells EZH2 prevented the premature expression of Cdkn2a and the consequent stabilization of p53, an effector of the pre-Ag receptor checkpoints. Deletion of Cdkn2a in EZH2-deficient lymphocytes prevented p53 stabilization, extended lymphocyte survival, and restored differentiation resulting in the generation of mature B and T lymphocytes. Our results uncover a crucial role for EZH2 in adaptive lymphocytes to control the developmental timing of effectors of the pre-Ag receptor checkpoints.

Original languageEnglish (US)
Pages (from-to)4682-4691
Number of pages10
JournalJournal of Immunology
Volume198
Issue number12
DOIs
StatePublished - Jun 15 2017

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Jacobsen, J. A., Woodard, J., Mandal, M., Clark, M. R., Bartom, E. T., Sigvardsson, M., & Kee, B. L. (2017). EZH2 regulates the developmental timing of effectors of the pre-Antigen receptor checkpoints. Journal of Immunology, 198(12), 4682-4691. https://doi.org/10.4049/jimmunol.1700319