EZH2 regulates the developmental timing of effectors of the pre-Antigen receptor checkpoints
(2017) In Journal of Immunology 198(12). p.4682-4691- 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... (More)
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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- author
- Jacobsen, Jennifer A. ; Woodard, Jennifer ; Mandal, Malay ; Clark, Marcus R. ; Bartom, Elizabeth T. ; Sigvardsson, Mikael LU and Kee, Barbara L.
- organization
- publishing date
- 2017-06-15
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 198
- issue
- 12
- pages
- 10 pages
- publisher
- American Association of Immunologists
- external identifiers
-
- scopus:85020479365
- wos:000405271300015
- pmid:28490575
- ISSN
- 0022-1767
- DOI
- 10.4049/jimmunol.1700319
- language
- English
- LU publication?
- yes
- id
- 94b457eb-9484-4ead-b2b2-26491e5a113b
- date added to LUP
- 2017-06-26 16:00:51
- date last changed
- 2024-05-26 18:05:31
@article{94b457eb-9484-4ead-b2b2-26491e5a113b,
abstract = {{<p>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.</p>}},
author = {{Jacobsen, Jennifer A. and Woodard, Jennifer and Mandal, Malay and Clark, Marcus R. and Bartom, Elizabeth T. and Sigvardsson, Mikael and Kee, Barbara L.}},
issn = {{0022-1767}},
language = {{eng}},
month = {{06}},
number = {{12}},
pages = {{4682--4691}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{EZH2 regulates the developmental timing of effectors of the pre-Antigen receptor checkpoints}},
url = {{http://dx.doi.org/10.4049/jimmunol.1700319}},
doi = {{10.4049/jimmunol.1700319}},
volume = {{198}},
year = {{2017}},
}