Journal article
A non-canonical function of Ezh2 preserves immune homeostasis
A Vasanthakumar, D Xu, ATL Lun, AJ Kueh, KPJM van Gisbergen, N Iannarella, X Li, L Yu, D Wang, BRG Williams, SCW Lee, IJ Majewski, DI Godfrey, GK Smyth, WS Alexander, MJ Herold, A Kallies, SL Nutt, RS Allan
EMBO Reports | WILEY | Published : 2017
Abstract
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We fur..
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Awarded by Northern California DX Foundation
Funding Acknowledgements
We thank David Tarlinton, Amanda Light, Simon Willis, Jane Visvader, Marnie Blewitt, and Sarah Kinkel from the Walter and Eliza Hall Institute and Nicholas Williamson (Bio21 University of Melbourne) for technical assistance, advice, and discussions. We also thank Alexander Tarakhovsky (Rockefeller University) for the Ezh2<SUP>fl/fl</SUP> mice and Stuart Orkin (DFCI, Harvard) for the Eed<SUP>fl/fl</SUP> mice. This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (RSA, SLN, WSA, GKS, AK, BRGW, DX, DIG), the Australian Research Council (RSA, SLN, AK), the Sylvia and Charles Viertel Foundation (AK), an American Asthma Foundation Grant (SLN, RSA), the National Natural Science Foundation of China (DX) (81273247, 81472655, and 31670905), the National Basic Research Program of China (2012CB911204), and the Netherlands Organization for Scientific Research (KPJvG). This study was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme and the Australian Cancer Research Fund.