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Identification of DNA Methyltransferase 3a as a T Cell Receptor-Induced Regulator of Th1 and Th2 Differentiation
Abstract
Ag-specific T cell cytokine expression is dictated by the context in which TCR engagement occurs. Recently it has become clear that epigenetic changes play a role in this process. DNA methyltransferase 3a (DNMT3a) is a de novo methyltransferase important to the epigenetic control of cell fate. We have determined that DNMT3a expression is increased following TCR engagement and that costimulation mitigates DNMT3a protein expression. T cells lacking DNMT3a simultaneously express IFN-γ and IL-4 after expansion under nonbiasing conditions. While global methylation of DNA from wild-type and knockout T cells is similar, DNMT3a-null T cells demonstrate selective hypomethylation of both the Il4 and Ifng loci after activation. Such hypomethylated knockout Th2 cells retain a greater capacity to express IFN-γ protein when they are subsequently exposed to Th1-biasing conditions. Based on these findings we propose that DNMT3a is a key participant in regulating T cell polarization at the molecular level by promoting stable selection of a context-specific cell fate through methylation of selective targets in T cells.
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“Similarly, DNMT3A localization to the Ifng promoter in T helper 2 (T H 2) cells, T helper 17 (T H 17) cells and regulatory T (T reg ) cells generated in vitro is associated with increased methylation and reduced Ifng expression; reduced Ifng methylation in DNMT3A-deficient T H 2, T H 17 and T reg cells leads to aberrant IFNγ production by all three subsets upon restimulation with the T H 1 cytok”
From Clonal haematopoiesis and dysregulation of the immune system (2023) · cites this paper as [167]
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Cites
Zheng, W.-P., & Flavell, R. A. (1997) · Cell · doi:10.1016/s0092-8674(00)80240-8 · Cited by 2,384
Research works printed but not linked: 39
- 2000, A novel transcription factor, T-bet, directs Th1 lineage commitment., 655
- 2006, The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells., 1121
- 2005, Regulatory T cell lineage specification by the forkhead transcription factor Foxp3., 329
- 2006, T helper cell differentiation: regulation by cis elements and epigenetics., 369
- 2006, Molecular enzymology of mammalian DNA methyltransferases., 203
- 2005, Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L., 13341
- 2008, Cyclical DNA methylation of a transcriptionally active promoter., 45
- 2001, Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia., 1172
- 2008, Decreased DNA methyltransferase 3A and 3B mRNA expression in peripheral blood mononuclear cells and increased plasma SAH concentration in adult patients with idiopathic thrombocytopenic purpura., 432
- 2008, Abnormal DNA methylation in T cells from patients with subacute cutaneous lupus erythematosus., 827
- 2008, Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus., 339
- 2006, Inhibition of IFN-γ transcription by site-specific methylation during T helper cell development., 2443
- 2004, A distinct region of the murine IFN-γ promoter is hypomethylated from early T cell development through mature naive and Th1 cell differentiation, but is hypermethylated in Th2 cells., 7377
- 1994, Differentiation of the T helper phenotypes by analysis of the methylation state of the IFN-γ gene., 3603
- 2007, Dynamic changes in histone-methylation “marks” across the locus encoding interferon-γ during the differentiation of T helper type 2 cells., 723
- 2007, Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-γ., 732
- 1998, Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation., 765
- 1998, Helper T cell differentiation is controlled by the cell cycle., 229
- 2002, Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene., 649
- 2007, Demethylation of a specific hypersensitive site in the Th2 locus control region., 17052
- 2001, A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival., 763
- 2002, Gene silencing quantitatively controls the function of a developmental trans-activator., 81
- 2007, Stat4 limits DNA methyltransferase recruitment and DNA methylation of the IL-18Rα gene during Th1 differentiation., 2052
- 2006, CpG sites preferentially methylated by Dnmt3a in vivo., 9901
- 2007, Identification of putative targets of DNA (cytosine-5) methylation-mediated transcriptional silencing using a novel conditionally active form of DNA methyltransferase 3a., 426
- 1999, DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development., 247
- 2007, De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells., 715
- 2005, Egr-2 and Egr-3 are negative regulators of T cell activation., 472
- 2001, TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27(Kip1)., 3737
- 2005, Increased protein stability causes DNA methyltransferase 1 dysregulation in breast cancer., 18302
- 2002, A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation., 38746
- 2004, Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting., 900
- 1996, Reversibility of T helper 1 and 2 populations is lost after long-term stimulation., 901
- 2007, MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B., 15805
- 2007, Superantigen-induced CD4+ T cell tolerance is associated with DNA methylation and histone hypo-acetylation at cytokine gene loci., 613
- 2004, DNA methylation is a nonredundant repressor of the Th2 effector program., 4402
- 2003, GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rβ2 chain or T-bet., 415
- 2005, STAT4 expression in human T cells is regulated by DNA methylation but not by promoter polymorphism., 7143
- 2004, Nuclear repositioning marks the selective exclusion of lineage-inappropriate transcription factor loci during T helper cell differentiation., 3604
Cited by
Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., et al. (2010) · Nature Genetics · doi:10.1038/ng.717 · Cited by 2,520
Role of donor clonal hematopoiesis in allogeneic hematopoietic stem-cell transplantation
Frick, M., Chan, W., Arends, C. M., Hablesreiter, R., Halik, A., Heuser, M., Michonneau, D., Blau, O., Hoyer, K., Christen, F., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2018.79.2184 · Cited by 223
Clonal haematopoiesis and dysregulation of the immune system
Belizaire, R., Wong, W. J., Robinette, M. L., & Ebert, B. L. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00843-3 · Cited by 161
Ladle, B. H., Li, K.-P., Phillips, M. J., Pucsek, A. B., Haile, A., Powell, J. D., Jaffee, E. M., Hildeman, D. A., & Gamper, C. J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1524490113 · Cited by 152
Self-citationDnmt3a restrains mast cell inflammatory responses
Leoni, C., Montagner, S., Rinaldi, A., Bertoni, F., Polletti, S., Balestrieri, C., & Monticelli, S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616420114 · Cited by 138
Metadata
- Authors
- Gamper, C. J., Agoston, A. T., Nelson, W. G., & Powell, J. D.
- Affiliations
- Department of Oncology, Johns Hopkins University, School of Medicine , Baltimore, MD 21231
- Department of Pathology, Brigham and Women’s Hospital , Boston, MA 02115
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08
- Volume
- 183
- Issue
- 4
- Pages
- 2267-2276
- ISSN
- 1550-6606
- 0022-1767
- PMC
- PMC2818975
- Cited by
- 100
- References
- 1
- Language
- en
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