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 language | English (US) |
|---|---|
| Pages (from-to) | 4682-4691 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 198 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 2017 |
Funding
This work was supported by grants from the National Institutes of Health (R21 AI109233, R01 AI106352) and a pilot project award from the University of Chicago Comprehensive Cancer Center (P30 CA014599). J.A.J. was supported by Medical Scientist Training Grant T32 GM007281, J.W. was supported by a fellowship from the Leukemia and Lymphoma Society, and B.L.K. was a Leukemia and Lymphoma Society scholar.
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology