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

Jacobsen, Jennifer A.; Woodard, Jennifer; Mandal, Malay; Clark, Marcus R.; Bartom, Elizabeth T.; Sigvardsson, Mikael LU and Kee, Barbara L. (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
organization
publishing date
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
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
2017-09-18 11:42:48
@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},
  volume       = {198},
  year         = {2017},
}