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Publication : EZH2 Regulates the Developmental Timing of Effectors of the Pre-Antigen Receptor Checkpoints.

First Author  Jacobsen JA Year  2017
Journal  J Immunol Volume  198
Issue  12 Pages  4682-4691
PubMed ID  28490575 Mgi Jnum  J:247865
Mgi Id  MGI:5926067 Doi  10.4049/jimmunol.1700319
Citation  Jacobsen JA, et al. (2017) EZH2 Regulates the Developmental Timing of Effectors of the Pre-Antigen Receptor Checkpoints. J Immunol 198(12):4682-4691
abstractText  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.
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