Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

An epigenetic view of helper T cell differentiation

Nature Immunology volume 4, pages 616–623 (2003)Cite this article

Abstract

Antigen and cytokine receptor signals act in synergy to direct the differentiation of CD4+ T cells. These signals initiate reciprocal activation and silencing of the interferon-γ (IFN-γ) and interleukin 4 (IL-4) cytokine gene loci, changes that are heritably maintained in the resulting T helper type 1 (TH1) or TH2 cells and their progeny. Early, unpolarized transcription and chromatin remodeling of the poised cytokine genes of naive T cells is followed by consolidation and spreading of epigenetic changes and the establishment of self-reinforcing transcription factor networks. Recent studies have begun to elucidate the molecular mechanisms that establish and maintain polarized cytokine gene expression, and thus the cellular identity of differentiated helper T cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Reciprocal regulation of transcription factor binding and chromatin remodeling at cis-regulatory regions.
Figure 2: Chromatin changes in the Il4 locus during commitment of naive T cells to the TH1 or TH2 lineage.
Figure 3: Transcription factor feedback loops direct polarization of cytokine gene expression.
Figure 4: A DNA-looping model to explain coordinate regulation of the linked TH2 cytokine genes Il4, Il5 and Il13.

Similar content being viewed by others

References

  1. Ahmad, K. & Henikoff, S. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol. Cell 9, 1191–1200 (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Turner, B.M. Cellular memory and the histone code. Cell 111, 285–291 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Fischle, W., Wang, Y. & Allis, C.D. Histone and chromatin cross-talk. Curr. Opin. Cell Biol. 15, 172–183 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Bird, A.P. & Wolffe, A.P. Methylation-induced repression: belts, braces, and chromatin. Cell 99, 451–454 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Tamaru, H. & Selker, E.U. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414, 277–283 (2001).

    Article  CAS  PubMed  Google Scholar 

  6. Grogan, J.L. & Locksley, R.M. T helper cell differentiation: on again, off again. Curr. Opin. Immunol. 14, 366–372 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Murphy, K.M. & Reiner, S.L. The lineage decisions of helper T cells. Nat. Rev. Immunol. 2, 933–944 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. Smale, S.T. & Fisher, A.G. Chromatin structure and gene regulation in the immune system. Annu. Rev. Immunol. 20, 427–462 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Avni, O. & Rao, A. T cell differentiation: a mechanistic view. Curr. Opin. Immunol. 12, 654–659 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Glimcher, L.H. & Murphy, K.M. Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 14, 1693–1711 (2000).

    CAS  PubMed  Google Scholar 

  11. Sad, S. & Mosmann, T.R. Single IL-2-secreting precursor CD4 T cell can develop into either TH1 or TH2 cytokine secretion phenotype. J. Immunol. 153, 3514–3522 (1994).

    CAS  PubMed  Google Scholar 

  12. Wang, X. & Mosmann, T. In vivo priming of CD4 T cells that produce interleukin (IL)-2 but not IL-4 or interferon (IFN)-γ, and can subsequently differentiate into IL-4- or IFN-γ-secreting cells. J. Exp. Med. 194, 1069–1080 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Messi, M. et al. Memory and flexibility of cytokine gene expression as separable properties of human TH1 and TH2 lymphocytes. Nat. Immunol. 4, 78–86 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Grogan, J.L. et al. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14, 205–215 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Gross, D.S. & Garrard, W.T. Nuclease hypersensitive sites in chromatin. Annu. Rev. Biochem. 57, 159–197 (1988).

    Article  CAS  PubMed  Google Scholar 

  16. Agarwal, S. & Rao, A. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, 765–775 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Takemoto, N. et al. TH2-specific DNAse I-hypersensitive sites in the murine IL-13 and IL-4 intergenic region. Int. Immunol. 10, 1981–1985 (1998).

    Article  CAS  PubMed  Google Scholar 

  18. Scotet, E., Schroeder, S. & Lanzavecchia, A. Molecular regulation of CC-chemokine receptor 3 expression in human T helper 2 cells. Blood 98, 2568–2570 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Hawwari, A., Burrows, J., Vadas, M.A. & Cockerill, P.N. The human IL-3 locus is regulated cooperatively by two NFAT-dependent enhancers that have distinct tissue-specific activities. J. Immunol. 169, 1876–1886 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Yui, M.A., Hernandez-Hoyos, G. & Rothenberg, E.V. A new regulatory region of the IL-2 locus that confers position-independent transgene expression. J. Immunol. 166, 1730–1739 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Lee, D.U., Agarwal, S. & Rao, A. TH2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16, 649–660 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. Takemoto, N. et al. Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for TH2-specific cytokine gene cluster. J. Immunol. 165, 6687–6691 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Agarwal, S., Avni, O. & Rao, A. Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 12, 643–652 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Weiss, D.L. & Brown, M.A. Regulation of IL-4 production in mast cells: a paradigm for cell-type-specific gene expression. Immunol. Rev. 179, 35–47 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Solymar, D.C., Agarwal, S., Bassing, C.H., Alt, F.W. & Rao, A. A 3′ enhancer in the IL-4 gene regulates cytokine production by TH2 cells and mast cells. Immunity 17, 41–50 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Pennacchio, L.A. & Rubin, E.M. Genomic strategies to identify mammalian regulatory sequences. Nat. Rev. Genet. 2, 100–109 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Loots, G.G. et al. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288, 136–140 (2000).

    Article  CAS  PubMed  Google Scholar 

  28. Mohrs, M. et al. Deletion of a coordinate regulator of type 2 cytokine expression in mice. Nat. Immunol. 2, 842–847 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Ellmeier, W., Sunshine, M.J., Losos, K. & Littman, D.R. Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in thymus-independent T cells. Immunity 9, 485–496 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Smith, C.L. & Hager, G.L. Transcriptional regulation of mammalian genes in vivo. A tale of two templates. J. Biol. Chem. 272, 27493–27496 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Hostert, A. et al. A region in the CD8 gene locus that directs expression to the mature CD8 T cell subset in transgenic mice. Immunity 7, 525–536 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Lee, G.R., Fields, P.E. & Flavell, R.A. Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 14, 447–459 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. Killeen, N., Sawada, S. & Littman, D.R. Regulated expression of human CD4 rescues helper T cell development in mice lacking expression of endogenous CD4. EMBO J. 12, 1547–1553 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sawada, S., Scarborough, J.D., Killeen, N. & Littman, D.R. A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development. Cell 77, 917–929 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Zou, Y.R. et al. Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage. Nat. Genet. 29, 332–336 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Siu, G., Wurster, A.L., Duncan, D.D., Soliman, T.M. & Hedrick, S.M. A transcriptional silencer controls the developmental expression of the CD4 gene. EMBO J. 13, 3570–3579 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Taniuchi, I., Sunshine, M.J., Festenstein, R. & Littman, D.R. Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation. Mol. Cell 10, 1083–1096 (2002).

    Article  CAS  PubMed  Google Scholar 

  38. Taniuchi, I. et al. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 111, 621–633 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Avni, O. et al. TH cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes. Nat. Immunol. 3, 643–651 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Fields, P.E., Kim, S.T. & Flavell, R.A. Cutting edge: changes in histone acetylation at the IL-4 and IFN-γ loci accompany TH1/TH2 differentiation. J. Immunol. 169, 647–650 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Peng, S.L., Gerth, A.J., Ranger, A.M. & Glimcher, L.H. NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity 14, 13–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Ranger, A.M., Oukka, M., Rengarajan, J. & Glimcher, L.H. Inhibitory function of two NFAT family members in lymphoid homeostasis and TH2 development. Immunity 9, 627–635 (1998).

    Article  CAS  PubMed  Google Scholar 

  43. Rengarajan, J., Tang, B. & Glimcher, L.H. NFATc2 and NFATc3 regulate TH2 differentiation and modulate TCR-responsiveness of naive TH cells. Nat. Immunol. 3, 48–54 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. Brogdon, J.L., Leitenberg, D. & Bottomly, K. The potency of TCR signaling differentially regulates NFATc/p activity and early IL-4 transcription in naive CD4+ T cells. J. Immunol. 168, 3825–3832 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Zhao, K. et al. Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95, 625–636 (1999).

    Article  Google Scholar 

  46. Shen, X., Xiao, H., Ranallo, R., Wu, W.H. & Wu, C. Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates. Science 299, 112–114 (2003).

    Article  CAS  PubMed  Google Scholar 

  47. Steger, D.J., Haswell, E.S., Miller, A.L., Wente, S.R. & O'Shea, E.K. Regulation of chromatin remodeling by inositol polyphosphates. Science 299, 114–116 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Chi, T.H. et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature 418, 195–199 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Bird, J.J. et al. Helper T cell differentiation is controlled by the cell cycle. Immunity 9, 229–237 (1998).

    Article  CAS  PubMed  Google Scholar 

  50. Lee, P.P. et al. A critical role for dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15, 763–774 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Hutchins, A.S. et al. Gene silencing quantitatively controls the function of a developmental trans-activator. Mol. Cell 10, 81–91 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Gett, A.V. & Hodgkin, P.D. Cell division regulates the T cell cytokine repertoire, revealing a mechanism underlying immune class regulation. Proc. Natl. Acad. Sci. USA 95, 9488–9493 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Richter, A., Lohning, M. & Radbruch, A. Instruction for cytokine expression in T helper lymphocytes in relation to proliferation and cell cycle progression. J. Exp. Med. 190, 1439–1450 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ben-Sasson, S.Z., Gerstel, R., Hu-Li, J. & Paul, W.E. Cell division is not a “clock” measuring acquisition of competence to produce IFN-γ or IL-4. J. Immunol. 166, 112–120 (2001).

    Article  CAS  PubMed  Google Scholar 

  55. Mullen, A.C. et al. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292, 1907–1910 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Lighvani, A.A. et al. T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells. Proc. Natl. Acad. Sci. USA 98, 15137–15142 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ouyang, W. et al. Stat6-independent GATA-3 autoactivation directs IL-4-independent TH2 development and commitment. Immunity 12, 27–37 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Szabo, S.J. et al. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295, 338–342 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Mullen, A.C. et al. Hlx is induced by and genetically interacts with T-bet to promote heritable TH1 gene induction. Nat. Immunol. 3, 652–658 (2002).

    Article  CAS  PubMed  Google Scholar 

  60. Afkarian, M. et al. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat. Immunol. 3, 549–557 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Szabo, S., Dighe, A., Gubler, U. & Murphy, K. Regulation of the interleukin (IL)-12R b2 subunit expression in developing T helper 1 (TH1) and TH2 cells. J. Exp. Med. 185, 817–824 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Szabo, S.J. et al. A novel transcription factor, T-bet, directs TH1 lineage commitment. Cell 100, 655–669 (2000).

    Article  CAS  PubMed  Google Scholar 

  63. Ouyang, W. et al. Inhibition of TH1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 9, 745–755 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Lee, H.J. et al. GATA-3 induces T helper cell type 2 (TH2) cytokine expression and chromatin remodeling in committed TH1 cells. J. Exp. Med. 192, 105–115 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ho, I.-C., Hodge, M.R., Rooney, J.W. & Glimcher, L.H. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85, 973–983 (1996).

    Article  CAS  PubMed  Google Scholar 

  66. Asnagli, H., Afkarian, M. & Murphy, K.M. Cutting edge: identification of an alternative GATA-3 promoter directing tissue-specific gene expression in mouse and human. J. Immunol. 168, 4268–4271 (2002).

    Article  CAS  PubMed  Google Scholar 

  67. Kurata, H. et al. Friend of GATA is expressed in naive TH cells and functions as a repressor of GATA-3-mediated TH2 cell development. J. Immunol. 168, 4538–4545 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Zhou, M. et al. Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells. J. Exp. Med. 194, 1461–1471 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Miaw, S.C., Choi, A., Yu, E., Kishikawa, H. & Ho, I.C. ROG, repressor of GATA, regulates the expression of cytokine genes. Immunity 12, 323–333 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Kelly, B.L. & Locksley, R.M. Coordinate regulation of the IL-4, IL-13, and IL-5 cytokine cluster in TH2 clones revealed by allelic expression patterns. J. Immunol. 165, 2982–2986 (2000).

    Article  CAS  PubMed  Google Scholar 

  71. Cousins, D.J., Lee, T.H. & Staynov, D.Z. Cytokine coexpression during human TH1/TH2 cell differentiation: direct evidence for coordinated expression of TH2 cytokines. J. Immunol. 169, 2498–2506 (2002).

    Article  CAS  PubMed  Google Scholar 

  72. Cohen, B.A., Mitra, R.D., Hughes, J.D. & Church, G.M. A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat. Genet. 26, 183–186 (2000).

    Article  CAS  PubMed  Google Scholar 

  73. Boutanaev, A.M., Kalmykova, A.I., Shevelyov, Y.Y. & Nurminsky, D.I. Large clusters of co-expressed genes in the Drosophila genome. Nature 420, 666–669 (2002).

    Article  CAS  PubMed  Google Scholar 

  74. Fransz, P., De Jong, J.H., Lysak, M., Castiglione, M.R. & Schubert, I. Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate. Proc. Natl. Acad. Sci. USA 99, 14584–14589 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yamashita, M. et al. Identification of a conserved GATA3 response element upstream proximal from the interleukin-13 gene locus. J. Biol. Chem. 277, 42399–42408 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Noma, K., Allis, C.D. & Grewal, S.I. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293, 1150–1155 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Litt, M.D., Simpson, M., Gaszner, M., Allis, C.D. & Felsenfeld, G. Correlation between histone lysine methylation and developmental changes at the chicken β-globin locus. Science 293, 2453–2455 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. Grosveld, F. Activation by locus control regions? Curr. Opin. Genet. Dev. 9, 152–157 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Adlam, M. & Siu, G. Hierarchical interactions control CD4 gene expression during thymocyte development. Immunity 18, 173–184 (2003).

    Article  CAS  PubMed  Google Scholar 

  80. Tolhuis, B., Palstra, R.J., Splinter, E., Grosveld, F. & de Laat, W. Looping and interaction between hypersensitive sites in the active β-globin locus. Mol. Cell 10, 1453–1465 (2002).

    Article  CAS  PubMed  Google Scholar 

  81. Carter, D., Chakalova, L., Osborne, C.S., Dai, Y.F. & Fraser, P. Long-range chromatin regulatory interactions in vivo. Nat. Genet. 32, 623–626 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Kosak, S.T. et al. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296, 158–162 (2002).

    Article  CAS  PubMed  Google Scholar 

  83. Schebesta, M., Heavey, B. & Busslinger, M. Transcriptional control of B-cell development. Curr. Opin. Immunol. 14, 216–223 (2002).

    Article  CAS  PubMed  Google Scholar 

  84. Horcher, M., Souabni, A. & Busslinger, M. Pax5/BSAP maintains the identity of B cells in late B lymphopoiesis. Immunity 14, 779–790 (2001).

    Article  CAS  PubMed  Google Scholar 

  85. Guo, L. et al. In TH2 cells the Il4 gene has a series of accessibility states associated with distinctive probabilities of IL-4 production. Proc. Natl. Acad. Sci. USA 99, 10623–10628 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhang, J., Xu, F., Hashimshony, T., Keshet, I. & Cedar, H. Establishment of transcriptional competence in early and late S phase. Nature 420, 198–202 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Rogan, D.F., Cousins, D.J. & Staynov, D.Z. Intergenic transcription occurs throughout the human IL-4/IL-13 gene cluster. Biochem. Biophys. Res. Commun. 255, 556–561 (1999).

    Article  CAS  PubMed  Google Scholar 

  88. Cohen, D.E. & Lee, J.T. X-chromosome inactivation and the search for chromosome-wide silencers. Curr. Opin. Genet. Dev. 12, 219–224 (2002).

    Article  CAS  PubMed  Google Scholar 

  89. Hall, I.M. et al. Establishment and maintenance of a heterochromatin domain. Science 297, 2232–2237 (2002).

    Article  CAS  PubMed  Google Scholar 

  90. Czermin, B. et al. Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111, 185–196 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Cao, R. et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039–1043 (2002).

    Article  CAS  PubMed  Google Scholar 

  92. Muller, J. et al. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111, 197–208 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Orlando, V. Polycomb, epigenomes, and control of cell identity. Cell 112, 599–606 (2003).

    Article  CAS  PubMed  Google Scholar 

  94. Kimura, M. et al. Regulation of TH2 cell differentiation by mel-18, a mammalian polycomb group gene. Immunity 15, 275–287 (2001).

    Article  CAS  PubMed  Google Scholar 

  95. Sweetser, M.T. et al. The roles of nuclear factor of activated T cells and yin-yang 1 in activation-induced expression of the interferon-γ promoter in T cells. J. Biol. Chem. 273, 34775–34783 (1998).

    Article  CAS  PubMed  Google Scholar 

  96. Guo, J. et al. Yin-Yang 1 activates interleukin-4 gene expression in T cells. J. Biol. Chem. 276, 48871–48878 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Bannister, A.J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120–124 (2001).

    Article  CAS  PubMed  Google Scholar 

  99. Festenstein, R. et al. Modulation of heterochromatin protein 1 dynamics in primary Mammalian cells. Science 299, 719–721 (2003).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank our colleagues for discussions. M.A. is supported by the Damon Runyon Cancer Research Fund (DRG-1682).

Author information

Authors and Affiliations

  1. Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    K Mark Ansel, Dong U Lee & Anjana Rao

Authors
  1. K Mark Ansel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dong U Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anjana Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anjana Rao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ansel, K., Lee, D. & Rao, A. An epigenetic view of helper T cell differentiation. Nat Immunol 4, 616–623 (2003). https://doi.org/10.1038/ni0703-616

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni0703-616

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing