Identification of DNA methyltransferase 3a as a T cell receptor-induced regulator of Th1 and Th2 differentiation

Journal of Immunology

Volumn 183, Issue 4, 2009, Pages 2267-2276

  Gamper, Christopher J ^a   Agoston, Agoston T ^b   Nelson, William G ^a   Powell, Jonathan D ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA METHYLTRANSFERASE 3A; GAMMA INTERFERON; INTERLEUKIN 2; INTERLEUKIN 4; T LYMPHOCYTE RECEPTOR; DNA (CYTOSINE 5) METHYLTRANSFERASE; LYMPHOCYTE ANTIGEN RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL DIFFERENTIATION; CELL FATE; CELL POLARITY; DNA METHYLATION; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENE LOCUS; IMMUNOBLOTTING; IMMUNOSTIMULATION; MASS SPECTROMETRY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TH1 CELL; TH2 CELL; WILD TYPE; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; CELL CULTURE; COMPARATIVE STUDY; CYTOLOGY; ENZYMOLOGY; GENETIC MARKER; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; MOUSE MUTANT; PHYSIOLOGY; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; UPREGULATION;

ANIMALS; CELL DIFFERENTIATION; CELLS, CULTURED; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; GENETIC MARKERS; INTERFERON-GAMMA; LYMPHOCYTE ACTIVATION; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; TH1 CELLS; TH2 CELLS; UP-REGULATION;

EID: 70149103640     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0802960     Document Type: Article

References (40)

1. Szabo, S. J., S. T. Kim, G. L. Costa, X. Zhang, C. G. Fathman, and L. H. Glimcher. 2000. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669.
2. Zheng, W., and R. A. Flavell. 1997. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89: 587-596. (Pubitemid 27511769)
3. + T helper cells. Cell 126: 1121-1133.
4. Fontenot, J. D., J. P. Rasmussen, L. M. Williams, J. L. Dooley, A. G. Farr, and A. Y. Rudensky. 2005. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 22: 329-341.
5. Lee, G. R., S. T. Kim, C. G. Spilianakis, P. E. Fields, and R. A. Flavell. 2006. T helper cell differentiation: regulation by cis elements and epigenetics. Immunity 24: 369-379.
6. Jeltsch, A. 2006. Molecular enzymology of mammalian DNA methyltransferases. Curr. Top. Microbiol. Immunol. 301: 203-225.
7. Gowher, H., K. Liebert, A. Hermann, G. Xu, and A. Jeltsch. 2005. Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J. Biol. Chem. 280: 13341-13348.
8. Metivier, R., R. Gallais, C. Tiffoche, C. Le Peron, R. Z. Jurkowska, R. P. Carmouche, D. Ibberson, P. Barath, F. Demay, G. Reid, et al. 2008. Cyclical DNA methylation of a transcriptionally active promoter. Nature 452: 45-50.
9. Mizuno, S., T. Chijiwa, T. Okamura, K. Akashi, Y. Fukumaki, Y. Niho, and H. Sasaki. 2001. Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood 97: 1172-1179.
10. Tao, J., M. Yang, Z. Chen, Y. Huang, Q. Zhao, J. Xu, H. Ren, H. Zhao, Z. Chen, Q. Ren, and R. Yang. 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. J. Clin. Immunol. 28: 432-439.
11. Luo, Y., Y. Li, Y. Su, H. Yin, N. Hu, S. Wang, and Q. Lu. 2008. Abnormal DNA methylation in T cells from patients with subacute cutaneous lupus erythematosus. Br. J. Dermatol. 159: 827-833.
12. + T cells from patients with systemic lupus erythematosus. Immunology 124: 339-347.
13. Jones, B., and J. Chen. 2006. Inhibition of IFN-γ transcription by site-specific methylation during T helper cell development. EMBO J. 25: 2443-2452.
14. Winders, B. R., R. H. Schwartz, and D. Bruniquel. 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. J. Immunol. 173: 7377-7384.
15. Young, H. A., P. Ghosh, J. Ye, J. Lederer, A. Lichtman, J. R. Gerard, L. Penix, C. B. Wilson, A. J. Melvin, M. E. McGurn, et al. 1994. Differentiation of the T helper phenotypes by analysis of the methylation state of the IFN-γ gene. J. Immunol. 153: 3603-3610.
16. Chang, S., and T. M. Aune. 2007. Dynamic changes in histone-methylation "marks" across the locus encoding interferon-γ during the differentiation of T helper type 2 cells. Nat. Immunol. 8: 723-731.
17. Schoenborn, J. R., M. O. Dorschner, M. Sekimata, D. M. Santer, M. Shnyreva, D. R. Fitzpatrick, J. A. Stamatoyannopoulos, and C. B. Wilson. 2007. Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-γ. Nat. Immunol. 8: 732-742.
18. Agarwal, S., and A. Rao. 1998. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9: 765-775.
19. Bird, J. J., D. R. Brown, A. C. Mullen, N. H. Moskowitz, M. A. Mahowald, J. R. Sider, T. F. Gajewski, C. R. Wang, and S. L. Reiner. 1998. Helper T cell differentiation is controlled by the cell cycle. Immunity 9: 229-237.
20. Lee, D. U., S. Agarwal, and A. Rao. 2002. Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16: 649-660.
21. Kim, S. T., P. E. Fields, and R. A. Flavell. 2007. Demethylation of a specific hypersensitive site in the Th2 locus control region. Proc. Natl. Acad. Sci. USA 104: 17052-17057.
22. Lee, P. P., D. R. Fitzpatrick, C. Beard, H. K. Jessup, S. Lehar, K. W. Makar, M. Perez-Melgosa, M. T. Sweetser, M. S. Schlissel, S. Nguyen, et al. 2001. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15: 763-774.
23. Hutchins, A. S., A. C. Mullen, H. W. Lee, K. J. Sykes, F. A. High, B. D. Hendrich, A. P. Bird, and S. L. Reiner. 2002. Gene silencing quantitatively controls the function of a developmental trans-activator. Mol. Cell. 10: 81-91.
24. Yu, Q., V. T. Thieu, and M. H. Kaplan. 2007. Stat4 limits DNA methyltransferase recruitment and DNA methylation of the IL-18Rα gene during Th1 differentiation. EMBO J. 26: 2052-2060.
25. Oka, M., N. Rodic, J. Graddy, L. J. Chang, and N. Terada. 2006. CpG sites preferentially methylated by Dnmt3a in vivo. J. Biol. Chem. 281: 9901-9908.
26. Samuel, M. S., T. Lundgren-May, and M. Ernst. 2007. Identification of putative targets of DNA (cytosine-5) methylation-mediated transcriptional silencing using a novel conditionally active form of DNA methyltransferase 3a. Growth Factors 25: 426-436.
27. Okano, M., D. W. Bell, D. A. Haber, and E. Li. 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99: 247-257.
28. Tadokoro, Y., H. Ema, M. Okano, E. Li, and H. Nakauchi. 2007. De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. J. Exp. Med. 204: 715-722.
29. Safford, M., S. Collins, M. A. Lutz, A. Allen, C. T. Huang, J. Kowalski, A. Blackford, M. R. Horton, C. Drake, R. H. Schwartz, and J. D. Powell. 2005. Egr-2 and Egr-3 are negative regulators of T cell activation. Nat. Immunol. 6: 472-480.
30. Powell, J. D., D. Bruniquel, and R. H. Schwartz. 2001. TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27(Kip1). Eur. J. Immunol. 31: 3737-3746.
31. Agoston, A. T., P. Argani, S. Yegnasubramanian, A. M. De Marzo, M. A. Ansari-Lari, J. L. Hicks, N. E. Davidson, and W. G. Nelson. 2005. Increased protein stability causes DNA methyltransferase 1 dysregulation in breast cancer. J. Biol. Chem. 280: 18302-18310.
32. Chen, T., Y. Ueda, S. Xie, and E. Li. 2002. A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation. J. Biol. Chem. 277: 38746-38754.
33. Kaneda, M., M. Okano, K. Hata, T. Sado, N. Tsujimoto, E. Li, and H. Sasaki. 2004. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429: 900-903.
34. Murphy, E., K. Shibuya, N. Hosken, P. Openshaw, V. Maino, K. Davis, K. Murphy, and A. O'Garra. 1996. Reversibility of T helper 1 and 2 populations is lost after long-term stimulation. J. Exp. Med. 183: 901-913.
35. Fabbri, M., R. Garzon, A. Cimmino, Z. Liu, N. Zanesi, E. Callegari, S. Liu, H. Alder, S. Costinean, C. Fernandez-Cymering, et al. 2007. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl. Acad. Sci. USA 104: 15805-15810.
36. + T cell tolerance is associated with DNA methylation and histone hypo-acetylation at cytokine gene loci. Genes Immun. 8: 613-618.
37. Makar, K. W., and C. B. Wilson. 2004. DNA methylation is a nonredundant repressor of the Th2 effector program. J. Immunol. 173: 4402-4406.
38. Usui, T., R. Nishikomori, A. Kitani, and W. Strober. 2003. GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rβ2 chain or T-bet. Immunity 18: 415-428. (Pubitemid 36351520)
39. Shin, H. J., H. Y. Park, S. J. Jeong, H. W. Park, Y. K. Kim, S. H. Cho, Y. Y. Kim, M. L. Cho, H. Y. Kim, K. U. Min, and C. W. Lee. 2005. STAT4 expression in human T cells is regulated by DNA methylation but not by promoter polymorphism. J. Immunol. 175: 7143-7150.
40. Hewitt, S. L., F. A. High, S. L. Reiner, A. G. Fisher, and M. Merkenschlager. 2004. Nuclear repositioning marks the selective exclusion of lineage-inappropriate transcription factor loci during T helper cell differentiation. Eur. J. Immunol. 34: 3604-3613.