DNA demethylation of the Foxp3 enhancer is maintained through modulation of ten-eleven-translocation and DNA methyltransferases

Molecules and Cells

Volumn 39, Issue 12, 2016, Pages 888-897

  Nair, Varun Sasidharan ^a   Song, Mi Hye ^a   Ko, Myunggon ^b   Oh, Kwon Ik ^a  

^a Hallym University College of Medicine   (South Korea)

^b Ulsan National Institute of Science and Technology   (South Korea)

Author keywords

Cytokine; DNA demethylation; Foxp3; Regulatory T cell; Ten Eleven Translocation (Tet)

Indexed keywords

DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE 1; GENOMIC DNA; INTERLEUKIN 6; MESSENGER RNA; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR FOXP3; DNA (CYTOSINE 5) METHYLTRANSFERASE; DNA (CYTOSINE-5-)-METHYLTRANSFERASE 1; DNA BINDING PROTEIN; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; INTERLEUKIN 2; ONCOPROTEIN; TET2 PROTEIN, MOUSE;

ADOPTIVE TRANSFER; ANIMAL CELL; ARTICLE; CD4+ T LYMPHOCYTE; CHROMATIN IMMUNOPRECIPITATION; CPG ISLAND; DEMETHYLATION; DNA EXTRACTION; DNA METHYLATION; ENHANCER REGION; GENETIC TRANSFECTION; IN VITRO STUDY; MALE; MOUSE; NONHUMAN; REGULATORY T LYMPHOCYTE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STABLE EXPRESSION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; GENETICS; METABOLISM; TRANSGENIC MOUSE;

ANIMALS; CPG ISLANDS; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; DNA MODIFICATION METHYLASES; DNA-BINDING PROTEINS; FORKHEAD TRANSCRIPTION FACTORS; INTERLEUKIN-2; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PROTO-ONCOGENE PROTEINS; T-LYMPHOCYTES, REGULATORY; TRANSFECTION;

EID: 85018391315     PISSN: 10168478     EISSN: 02191032     Source Type: Journal    
DOI: 10.14348/molcells.2016.0276     Document Type: Article

References (41)

1. Burzyn, D., Kuswanto, W., Kolodin, D., Shadrach, J.L., Cerletti, M., Jang, Y., Sefik, E., Tan, T.G., Wagers, A.J., Benoist, C., et al. (2013). A special population of regulatory T cells potentiates muscle repair. Cell 155, 1282-1295.
2. Campbell, D.J., and Koch, M.A. (2011). Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat. Rev. Immunol. 11, 119-130.
3. Chaudhry, A., Rudra, D., Treuting, P., Samstein, R.M., Liang, Y., Kas, A., and Rudensky, A.Y. (2009). CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326, 986-991.
4. Chung, Y., Tanaka, S., Chu, F., Nurieva, R.I., Martinez, G.J., Rawal, S., Wang, Y.H., Lim, H., Reynolds, J.M., Zhou, X.H., et al. (2011). Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat. Med. 17, 983-988.
5. Cipolletta, D., Feuerer, M., Li, A., Kamei, N., Lee, J., Shoelson, S.E., Benoist, C., and Mathis, D. (2012). PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486, 549-553.
6. Dickson, K.M., Gustafson, C.B., Young, J.I., Zuchner, S., and Wang, G. (2013). Ascorbate-induced generation of 5-hydroxymethylcytosine is unaffected by varying levels of iron and 2-oxoglutarate. Biochem. Biophys. Res. Commun. 439, 522-527.
7. Feng, Y., Arvey, A., Chinen, T., van der Veeken, J., Gasteiger, G., and Rudensky, A.Y. (2014). Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus. Cell 158, 749-763.
8. Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J., Schlawe, K., Chang, H.D., Bopp, T., Schmitt, E., et al. (2007). Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 5, e38.
9. Fontenot, J.D., Gavin, M.A., and Rudensky, A.Y. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330-336.
10. Han, J.A., An, J., and Ko, M. (2015). Functions of TET proteins in hematopoietic transformation. Mol. Cells 38, 925-935.
11. Hansmann, L., Schmidl, C., Boeld, T.J., Andreesen, R., Hoffmann, P., Rehli, M., and Edinger, M. (2010). Isolation of intact genomic DNA from FOXP3-sorted human regulatory T cells for epigenetic analyses. Eur. J. Immunol. 40, 1510-1512.
12. Hori, S., Nomura, T., and Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061.
13. Huehn, J., and Beyer, M. (2015). Epigenetic and transcriptional control of Foxp3+ regulatory T cells. Semin. Immunol. 27, 10-18.
14. Huehn, J., Polansky, J.K., and Hamann, A. (2009). Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat. Rev. Immunol. 9, 83-89.
15. Jeltsch, A., and Jurkowska, R.Z. (2014). New concepts in DNA methylation. Trends Biochem. Sci. 39, 310-318.
16. Josefowicz, S.Z., Wilson, C.B., and Rudensky, A.Y. (2009). Cutting edge: TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1. J. Immunol. 182, 6648-6652.
17. Kim, H.P., and Leonard, W.J. (2007). CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 204, 1543-1551.
18. Kim, K.Y., Lee, G., Yoon, M., Cho, E.H., Park, C.S., and Kim, M.G. (2015). Expression analyses revealed thymic stromal cotransporter/ Slc46A2 is in stem cell populations and is a putative tumor suppressor. Mol. Cells 38, 548-561.
19. Ko, M., Huang, Y., Jankowska, A.M., Pape, U.J., Tahiliani, M., Bandukwala, H.S., An, J., Lamperti, E.D., Koh, K.P., Ganetzky, R., et al. (2010). Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468, 839-843.
20. Koch, M.A., Tucker-Heard, G., Perdue, N.R., Killebrew, J.R., Urdahl, K.B., and Campbell, D.J. (2009). The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat. Immunol. 10, 595-602.
21. Li, X., Liang, Y., LeBlanc, M., Benner, C., and Zheng, Y. (2014). Function of a Foxp3 cis-element in protecting regulatory T cell identity. Cell 158, 734-748.
22. Linterman, M.A., Pierson, W., Lee, S.K., Kallies, A., Kawamoto, S., Rayner, T.F., Srivastava, M., Divekar, D.P., Beaton, L., Hogan, J.J., et al. (2011). Foxp3+ follicular regulatory T cells control the germinal center response. Nat. Med. 17, 975-982.
23. Malek, T.R. (2008). The biology of interleukin-2. Annu. Rev. Immunol. 26, 453-479.
24. Mantei, A., Rutz, S., Janke, M., Kirchhoff, D., Jung, U., Patzel, V., Vogel, U., Rudel, T., Andreou, I., Weber, M., et al. (2008). siRNA stabilization prolongs gene knockdown in primary T lymphocytes. Eur. J. Immunol. 38, 2616-2625.
25. Miyao, T., Floess, S., Setoguchi, R., Luche, H., Fehling, H.J., Waldmann, H., Huehn, J., and Hori, S. (2012). Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity 36, 262-275.
26. Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M.E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011). Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20, 11-24.
27. Ohkura, N., Hamaguchi, M., Morikawa, H., Sugimura, K., Tanaka, A., Ito, Y., Osaki, M., Tanaka, Y., Yamashita, R., Nakano, N., et al. (2012). T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 37, 785-799.
28. Ohnmacht, C., Park, J.H., Cording, S., Wing, J.B., Atarashi, K., Obata, Y., Gaboriau-Routhiau, V., Marques, R., Dulauroy, S., Fedoseeva, M., et al. (2015). MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORgammat(+) T cells. Science 349, 989-993.
29. Piper, C., Pesenacker, A.M., Bending, D., Thirugnanabalan, B., Varsani, H., Wedderburn, L.R., and Nistala, K. (2014). T cell expression of granulocyte-macrophage colony-stimulating factor in juvenile arthritis is contingent upon Th17 plasticity. Arthritis Rheumatol. 66, 1955-1960.
30. Polansky, J.K., Kretschmer, K., Freyer, J., Floess, S., Garbe, A., Baron, U., Olek, S., Hamann, A., von Boehmer, H., and Huehn, J. (2008). DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 38, 1654-1663.
31. Sakaguchi, S., Vignali, D.A., Rudensky, A.Y., Niec, R.E., and Waldmann, H. (2013). The plasticity and stability of regulatory T cells. Nat. Rev. Immunol. 13, 461-467.
32. Sasidharan Nair, V., Song, M.H., and Oh, K.I. (2016). Vitamin C Facilitates Demethylation of the Foxp3 Enhancer in a Tet-Dependent Manner. J. Immunol. 196, 2119-2131.
33. Sefik, E., Geva-Zatorsky, N., Oh, S., Konnikova, L., Zemmour, D., McGuire, A.M., Burzyn, D., Ortiz-Lopez, A., Lobera, M., Yang, J., et al. (2015). MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of RORgamma(+) regulatory T cells. Science 349, 993-997.
34. Toker, A., Engelbert, D., Garg, G., Polansky, J.K., Floess, S., Miyao, T., Baron, U., Duber, S., Geffers, R., Giehr, P., et al. (2013). Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. J. Immunol. 190, 3180-3188.
35. Wang, Y., Su, M.A., and Wan, Y.Y. (2011). An essential role of the transcription factor GATA-3 for the function of regulatory T cells. Immunity 35, 337-348.
36. Wang, L., Liu, Y., Beier, U.H., Han, R., Bhatti, T.R., Akimova, T., and Hancock, W.W. (2013). Foxp3+ T-regulatory cells require DNA methyltransferase 1 expression to prevent development of lethal autoimmunity. Blood 121, 3631-3639.
37. Wieczorek, G., Asemissen, A., Model, F., Turbachova, I., Floess, S., Liebenberg, V., Baron, U., Stauch, D., Kotsch, K., Pratschke, J., et al. (2009). Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res. 69, 599-608.
38. Yang, X.P., Ghoreschi, K., Steward-Tharp, S.M., Rodriguez-Canales, J., Zhu, J., Grainger, J.R., Hirahara, K., Sun, H.W., Wei, L., Vahedi, G., et al. (2011). Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat. Immunol. 12, 247-254.
39. Yang, R., Qu, C., Zhou, Y., Konkel, J.E., Shi, S., Liu, Y., Chen, C., Liu, S., Liu, D., Chen, Y., et al. (2015). Hydrogen Sulfide Promotes Tet1-and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis. Immunity 43, 251-263.
40. Yue, X., Trifari, S., Aijo, T., Tsagaratou, A., Pastor, W.A., Zepeda-Martinez, J.A., Lio, C.W., Li, X., Huang, Y., Vijayanand, P., et al. (2016). Control of Foxp3 stability through modulation of TET activity. J. Exp. Med. 213, 377-397.
41. Zheng, Y., Josefowicz, S., Chaudhry, A., Peng, X.P., Forbush, K., and Rudensky, A.Y. (2010). Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463, 808-812.