Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

GATA-3

  • Anuradha Ray
  • Anupriya Khare
  • Nandini Krishnamoorthy
  • Prabir Ray
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_29

Synonyms

Historical Background

Cellular fate during development, differentiation, and function is tightly regulated and orchestrated in a hierarchical fashion by transcriptional activators and repressors. GATA-3 is one such master regulator of cellular fate, which was identified in 1990 along with two other GATA-family members and was found to be abundantly expressed in T lymphocytes and the brain (Yamamoto et al. 1990). GATA-3 was first described as a transcription factor that interacts with the TCR-α gene enhancer (Ho et al. 1991). It belongs to the GATA family of transcription factors that are conserved proteins containing one or two C2-C2 type zinc fingers and a highly conserved C4 zinc finger that recognizes a consensus DNA sequence A/TGATAA/G from which the name of the family originated (Merika and Orkin 1993; Labastie et al. 1994). The mammalian GATA family of transcription factors consists of six members: GATA-binding protein 1 (GATA-1)–GATA-6. These...

This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was supported by National Institutes of Health grants AI048927, AI106684 and HL113956 (to A.R.), and AI100012 and HL122307 (to P.R.).

References

  1. Agarwal S, et al. Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 2000;12(6):643–652.PubMedCrossRefGoogle Scholar
  2. Amsen D, et al. Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 2007;27(1):89–99.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Anderson MK, et al. Definition of regulatory network elements for T cell development by perturbation analysis with PU.1 and GATA-3. Dev Biol 2002;246(1):103–121.PubMedCrossRefGoogle Scholar
  4. Asselin-Labat ML, et al. Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 2007;9(2):201–209.PubMedCrossRefGoogle Scholar
  5. Bernink JH, et al. The role of ILC2 in pathology of type 2 inflammatory diseases. Curr Opin Immunol 2014;31:115–120.PubMedCrossRefGoogle Scholar
  6. Bour-Jordan H, et al. CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage commitment. Nat Immunol 2003;4(2):182–188.PubMedCrossRefGoogle Scholar
  7. Chang JE, et al. Prostaglandin D2 regulates human type 2 innate lymphoid cell chemotaxis. J Allergy Clin Immunol 2014;133(3):899–901 e3.PubMedCrossRefGoogle Scholar
  8. Chen D, Zhang G. Enforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis. Exp Hematol 2001;29(8):971–980.PubMedCrossRefGoogle Scholar
  9. Chen CH, et al. Cyclic AMP activates p38 mitogen-activated protein kinase in Th2 cells: phosphorylation of GATA-3 and stimulation of Th2 cytokine gene expression. J Immunol 2000;165(10):5597–5605.PubMedCrossRefGoogle Scholar
  10. Chou J, et al. GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol 2010;222(1):42–49.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Das J, et al. A critical role for NF-kB in Gata3 expression and Th2 differentiation in allergic airway inflammation. Nat Immunol 2001;2:45–50.PubMedCrossRefGoogle Scholar
  12. David-Fung ES, et al. Progression of regulatory gene expression states in fetal and adult pro-T-cell development. Immunol Rev 2006;209:212–236.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Debacker C, et al. Embryonic expression of the human GATA-3 gene. Mech Dev 1999;85(1–2):183–187.PubMedCrossRefGoogle Scholar
  14. Dent AL, et al. T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6. Proc Natl Acad Sci USA 1998;95(23):13823–13828.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Djuretic IM, et al. Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat Immunol 2007;8(2):145–153.PubMedCrossRefGoogle Scholar
  16. Ferber IA, et al. GATA-3 significantly downregulates IFN-gamma production from developing Th1 cells in addition to inducing IL-4 and IL-5 levels. Clin Immunol 1999;91(2):134–144.PubMedCrossRefGoogle Scholar
  17. Finotto S, et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J Exp Med 2001;193(11):1247–1260.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Finotto S, et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 2002;295(5553):336–338.PubMedCrossRefGoogle Scholar
  19. George KM, et al. Embryonic expression and cloning of the murine GATA-3 gene. Development 1994;120(9):2673–2686.PubMedGoogle Scholar
  20. Grogan JL, et al. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 2001;14(3):205–215.PubMedCrossRefGoogle Scholar
  21. Hattori N, et al. Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus. J Exp Med 1996;184(3):1137–1147.PubMedCrossRefGoogle Scholar
  22. Hendriks RW, et al. Expression of the transcription factor GATA-3 is required for the development of the earliest T cell progenitors and correlates with stages of cellular proliferation in the thymus. Eur J Immunol 1999;29(6):1912–1918.PubMedCrossRefGoogle Scholar
  23. Hernandez-Hoyos G, et al. GATA-3 expression is controlled by TCR signals and regulates CD4/CD8 differentiation. Immunity 2003;19(1):83–94.PubMedCrossRefGoogle Scholar
  24. Hirahara K, et al. Repressor of GATA regulates TH2-driven allergic airway inflammation and airway hyperresponsiveness. J Allergy Clin Immunol 2008;122(3):512–520 e11.PubMedCrossRefGoogle Scholar
  25. Ho IC, Pai SY. GATA-3 - not just for Th2 cells anymore. Cell Mol Immunol 2007;4(1):15–29.PubMedGoogle Scholar
  26. Ho IC, et al. Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene. EMBO J 1991;10(5):1187–1192.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Homburg U, et al. Safety and tolerability of a novel inhaled GATA3 mRNA targeting DNAzyme in patients with TH2-driven asthma. J Allergy Clin Immunol 2015;136(3):797–800.PubMedCrossRefGoogle Scholar
  28. Hosoya T, et al. GATA-3 is required for early T lineage progenitor development. J Exp Med 2009;206(13):2987–3000.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Hosoya T, et al. From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation. Immunol Rev 2010;238(1):110–125.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Hoyler T, et al. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 2012;37(4):634–648.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Hwang ES, et al. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 2005;307(5708):430–433.PubMedCrossRefGoogle Scholar
  32. Kaufman CK, et al. GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev 2003;17(17):2108–2122.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Kim PJ, et al. GATA-3 regulates the development and function of invariant NKT cells. J Immunol 2006;177(10):6650–6659.PubMedCrossRefGoogle Scholar
  34. Kinjo Y, Kronenberg M. V alpha14 i NKT cells are innate lymphocytes that participate in the immune response to diverse microbes. J Clin Immunol 2005;25(6):522–533.PubMedCrossRefGoogle Scholar
  35. Ko LJ, et al. Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer. Mol Cell Biol 1991;11(5):2778–2784.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Kouros-Mehr H, et al. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell 2006;127(5):1041–1055.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Kouros-Mehr H, et al. GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell 2008;13(2):141–152.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Krishnamoorthy N, et al. Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma. Nat Med 2012;18(10):1525–1530.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Krug N, et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med 2015;372(21):1987–1995.PubMedCrossRefGoogle Scholar
  40. Kuo CT, et al. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev 1997;11(8):1048–1060.PubMedCrossRefGoogle Scholar
  41. Labastie MC, et al. Structure and expression of the human GATA3 gene. Genomics 1994;21(1):1–6.PubMedCrossRefGoogle Scholar
  42. Labastie MC, et al. The GATA-3 gene is expressed during human kidney embryogenesis. Kidney Int 1995;47(6):1597–1603.PubMedCrossRefGoogle Scholar
  43. Lee HJ, et al. Characterization of cis-regulatory elements and nuclear factors conferring Th2-specific expression of the IL-5 gene: a role for a GATA-binding protein. J Immunol 1998;160(5):2343–2352.PubMedGoogle Scholar
  44. Lloyd CM, Saglani S. Epithelial cytokines and pulmonary allergic inflammation. Curr Opin Immunol 2015;34:52–58.PubMedCrossRefGoogle Scholar
  45. Lowry JA, Atchley WR. Molecular evolution of the GATA family of transcription factors: conservation within the DNA-binding domain. J Mol Evol 2000;50(2):103–115.PubMedCrossRefGoogle Scholar
  46. Maneechotesuwan K, et al. Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. J Immunol 2007;178(4):2491–2498.PubMedCrossRefGoogle Scholar
  47. Maneechotesuwan K, et al. Suppression of GATA-3 nuclear import and phosphorylation: a novel mechanism of corticosteroid action in allergic disease. PLoS Med 2009;6(5):e1000076.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Martinez-Gonzalez I, et al. Lung ILC2s link innate and adaptive responses in allergic inflammation. Trends Immunol 2015;36(3):189–195.PubMedCrossRefGoogle Scholar
  49. Merika M, Orkin SH. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol 1993;13(7):3999–4010.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Miaw SC, et al. ROG, repressor of GATA, regulates the expression of cytokine genes. Immunity 2000;12(3):323–333.PubMedCrossRefGoogle Scholar
  51. Nakamura Y, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J Allergy Clin Immunol 1999;103(2 Pt 1):215–222.PubMedCrossRefGoogle Scholar
  52. Naoe Y, et al. Repression of interleukin-4 in T helper type 1 cells by Runx/Cbf beta binding to the Il4 silencer. J Exp Med 2007;204(8):1749–1755.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Oosterwegel M, et al. Expression of GATA-3 during lymphocyte differentiation and mouse embryogenesis. Dev Immunol 1992;3(1):1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Ouyang W, et al. Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 1998;9(5):745–755.PubMedCrossRefGoogle Scholar
  55. Ouyang W, et al. Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 2000;12(1):27–37.PubMedCrossRefGoogle Scholar
  56. Pai SY, et al. Critical roles for transcription factor GATA-3 in thymocyte development. Immunity 2003;19(6):863–875.PubMedCrossRefGoogle Scholar
  57. Pai SY, et al. GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells. Proc Natl Acad Sci USA 2004;101(7):1993–1998.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Pai SY, et al. Distinct structural requirements of GATA-3 for the regulation of thymocyte and Th2 cell differentiation. J Immunol 2008;180(2):1050–1059.PubMedCrossRefGoogle Scholar
  59. Pandolfi PP, et al. Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 1995;11(1):40–44.PubMedCrossRefGoogle Scholar
  60. Raundhal M, et al. High IFN-gamma and low SLPI mark severe asthma in mice and humans. J Clin Invest 2015;125(8):3037–3050.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Ray A, Cohn L. Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J Clin Invest 1999;104(8):985–993.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Robinson DS, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992;326(5):298–304.PubMedCrossRefGoogle Scholar
  63. Rudra D, et al. Transcription factor Foxp3 and its protein partners form a complex regulatory network. Nat Immunol 2012;13(10):1010–1019.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Samson SI, et al. GATA-3 promotes maturation, IFN-gamma production, and liver-specific homing of NK cells. Immunity 2003;19(5):701–711.PubMedCrossRefGoogle Scholar
  65. Sherman MA, et al. STAT6-independent production of IL-4 by mast cells. Eur J Immunol 1999;29(4):1235–1242.PubMedCrossRefGoogle Scholar
  66. Siegel MD, et al. Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE0 elements. J Biol Chem 1995;270(41):24548–24555.PubMedCrossRefGoogle Scholar
  67. Sigurs N, et al. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000;161(5):1501–1507.PubMedCrossRefGoogle Scholar
  68. Simon MC. Gotta have GATA. Nat Genet 1995;11(1):9–11.PubMedCrossRefGoogle Scholar
  69. Skapenko A, et al. GATA-3 in human T cell helper type 2 development. J Exp Med 2004;199(3):423–428.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Solymar DC, et al. A 3′ enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cells. Immunity 2002;17(1):41–50.PubMedCrossRefGoogle Scholar
  71. Szabo SJ, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000;100(6):655–669.PubMedCrossRefGoogle Scholar
  72. Taghon T, et al. Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3. Nat Immunol 2007;8(8):845–855.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Takahashi S, et al. Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vivo. Blood 1998;92(2):434–442.PubMedGoogle Scholar
  74. Tindemans I, et al. GATA-3 function in innate and adaptive immunity. Immunity 2014;41(2):191–206.PubMedCrossRefGoogle Scholar
  75. Ting CN, et al. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 1996;384(6608):474–478.PubMedCrossRefGoogle Scholar
  76. Tong Q, et al. Function of GATA transcription factors in preadipocyte-adipocyte transition. Science 2000;290(5489):134–138.PubMedCrossRefGoogle Scholar
  77. Tsai FY, et al. An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 1994;371(6494):221–226.CrossRefGoogle Scholar
  78. Tydell CC, et al. Molecular dissection of prethymic progenitor entry into the T lymphocyte developmental pathway. J Immunol 2007;179(1):421–438.PubMedCrossRefGoogle Scholar
  79. Usui T, et al. GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Immunity 2003;18(3):415–428.PubMedCrossRefGoogle Scholar
  80. Usui T, et al. T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 2006;203(3):755–766.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Van Esch H, Devriendt K. Transcription factor GATA3 and the human HDR syndrome. Cell Mol Life Sci 2001;58(9):1296–1300.PubMedCrossRefGoogle Scholar
  82. Walker C, et al. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 1992;146(1):109–115.PubMedCrossRefGoogle Scholar
  83. Wang ZY, et al. Regulation of Th2 cytokine expression in NKT cells: unconventional use of Stat6, GATA-3, and NFAT2. J Immunol 2006;176(2):880–888.PubMedCrossRefGoogle Scholar
  84. Wang Y, et al. An essential role of the transcription factor GATA-3 for the function of regulatory T cells. Immunity 2011;35(3):337–348.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Wohlfert EA, et al. GATA3 controls Foxp3(+) regulatory T cell fate during inflammation in mice. J Clin Invest 2011;121(11):4503–4515.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Wu P, et al. Evidence of a causal role of winter virus infection during infancy in early childhood asthma. Am J Respir Crit Care Med 2008;178(11):1123–1129.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Xue L, et al. Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol 2014;133(4):1184–1194.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Yamamoto M, et al. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev 1990;4(10):1650–1662.PubMedCrossRefGoogle Scholar
  89. Yamane H, et al. Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment. J Exp Med 2005;202(6):793–804.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Yamashita M, et al. Ras-ERK MAPK cascade regulates GATA3 stability and Th2 differentiation through ubiquitin-proteasome pathway. J Biol Chem 2005;280(33):29409–29419.PubMedCrossRefGoogle Scholar
  91. Yang Z, et al. Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains. Mol Cell Biol 1994;14(3):2201–2212.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Yu F, et al. Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance. Nat Immunol 2015;16(2):197–206.PubMedCrossRefGoogle Scholar
  93. Zhang DH, et al. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem 1997;272(34):21597–21603.PubMedCrossRefGoogle Scholar
  94. Zhang DH, et al. Differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3. J Immunol 1998;161(8):3817–3821.PubMedGoogle Scholar
  95. Zhang DH, et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 1999;11(4):473–482.PubMedCrossRefGoogle Scholar
  96. Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 1997;89(4):587–596.PubMedCrossRefGoogle Scholar
  97. Zhu J, et al. Stat5 activation plays a critical role in Th2 differentiation. Immunity 2003;19(5):739–748.PubMedCrossRefGoogle Scholar
  98. Zhu J, et al. Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nat Immunol 2004;5(11):1157–1165.PubMedCrossRefGoogle Scholar
  99. Zhu J, et al. GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res 2006;16(1):3–10.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Anuradha Ray
    • 1
  • Anupriya Khare
    • 1
  • Nandini Krishnamoorthy
    • 2
  • Prabir Ray
    • 1
  1. 1.Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and Department of ImmunologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Division of Pulmonary, Allergy and Critical Care Medicine, Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA