Ho, I.C. & Glimcher, L.H. Transcription: tantalizing times for T cells. Cell 109 Suppl., S109–S120 (2002).
Murphy, K.M. & Reiner, S.L. The lineage decisions of helper T cells. Nat. Rev. Immunol. 2, 933–944 (2002).
Ansel, K.M., Lee, D.U. & Rao, A. An epigenetic view of helper T cell differentiation. Nat. Immunol. 4, 616–623 (2003).
Szabo, S.J., Sullivan, B.M., Peng, S.L. & Glimcher, L.H. Molecular mechanisms regulating Th1 immune responses. Annu. Rev. Immunol. 21, 713–758 (2003).
Hwang, E.S., Szabo, S.J., Schwartzberg, P.L. & Glimcher, L.H. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307, 430–433 (2005).
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. 203, 755–766 (2006).
Mullen, A.C. et al. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292, 1907–1910 (2001).
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).
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).
Lee, G.R., Kim, S.T., Spilianakis, C.G., Fields, P.E. & Flavell, R.A. T helper cell differentiation: regulation by cis elements and epigenetics. Immunity 24, 369–379 (2006).
Young, H.A. et al. Expression of human IFN-γ genomic DNA in transgenic mice. J. Immunol. 143, 2389–2394 (1989).
Zhu, H. et al. Unexpected characteristics of the IFN-γ reporters in nontransformed T cells. J. Immunol. 167, 855–865 (2001).
Soutto, M., Zhou, W. & Aune, T.M. Cutting edge: distal regulatory elements are required to achieve selective expression of IFN-γ in Th1/Tc1 effector cells. J. Immunol. 169, 6664–6667 (2002).
Gaszner, M. & Felsenfeld, G. Insulators: exploiting transcriptional and epigenetic mechanisms. Nat. Rev. Genet. 7, 703–713 (2006).
Valenzuela, L. & Kamakaka, R.T. Chromatin insulators. Annu. Rev. Genet. 40, 107–138 (2006).
West, A.G. & Fraser, P. Remote control of gene transcription. Hum. Mol. Genet. 14, R101–11 (2005).
Nardone, J., Lee, D.U., Ansel, K.M. & Rao, A. Bioinformatics for the `bench biologist': how to find regulatory regions in genomic DNA. Nat. Immunol. 5, 768–774 (2004).
Dorschner, M.O. et al. High-throughput localization of functional elements by quantitative chromatin profiling. Nat. Methods 1, 219–225 (2004).
Igawa, D., Sakai, M. & Savan, R. An unexpected discovery of two interferon gamma-like genes along with interleukin (IL)-22 and -26 from teleost: IL-22 and -26 genes have been described for the first time outside mammals. Mol. Immunol. 43, 999–1009 (2006).
Dumoutier, L., Van Roost, E., Ameye, G., Michaux, L. & Renauld, J.C. IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes. Genes Immun. 1, 488–494 (2000).
Vigneau, S., Rohrlich, P.S., Brahic, M. & Bureau, J.F. Tmevpg1, a candidate gene for the control of Theiler's virus persistence, could be implicated in the regulation of gamma interferon. J. Virol. 77, 5632–5638 (2003).
Lee, D.U., Avni, O., Chen, L. & Rao, A. A distal enhancer in the interferon-γ (IFN- γ) locus revealed by genome sequence comparison. J. Biol. Chem. 279, 4802–4810 (2004).
Shnyreva, M. et al. Evolutionarily conserved sequence elements that positively regulate IFN-γ expression in T cells. Proc. Natl. Acad. Sci. USA 101, 12622–12627 (2004).
Bernstein, B.E. et al. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120, 169–181 (2005).
Agarwal, S. & Rao, A. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, 765–775 (1998).
Schneider, R. et al. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat. Cell Biol. 6, 73–77 (2004).
Cao, R. et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039–1043 (2002).
Bracken, A.P., Dietrich, N., Pasini, D., Hansen, K.H. & Helin, K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 20, 1123–1136 (2006).
Lee, C.K., Shibata, Y., Rao, B., Strahl, B.D. & Lieb, J.D. Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat. Genet. 36, 900–905 (2004).
Chen, X., Wang, J., Woltring, D., Gerondakis, S. & Shannon, M.F. Histone dynamics on the interleukin-2 gene in response to T-cell activation. Mol. Cell. Biol. 25, 3209–3219 (2005).
Simon, J.A. & Tamkun, J.W. Programming off and on states in chromatin: mechanisms of Polycomb and trithorax group complexes. Curr. Opin. Genet. Dev. 12, 210–218 (2002).
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).
Makar, K.W. et al. Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells. Nat. Immunol. 4, 1183–1190 (2003).
Zhong, X.P. & Krangel, M.S. An enhancer-blocking element between α and δ gene segments within the human T cell receptor α/δ locus. Proc. Natl. Acad. Sci. USA 94, 5219–5224 (1997).
Gombert, W.M. et al. The c-myc insulator element and matrix attachment regions define the c-myc chromosomal domain. Mol. Cell. Biol. 23, 9338–9348 (2003).
Grogan, J.L. & Locksley, R.M. T helper cell differentiation: on again, off again. Curr. Opin. Immunol. 14, 366–372 (2002).
Avni, O. et al. TH cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes. Nat. Immunol. 3, 643–651 (2002).
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).
Spilianakis, C.G., Lalioti, M.D., Town, T., Lee, G.R. & Flavell, R.A. Interchromosomal associations between alternatively expressed loci. Nature 435, 637–645 (2005).
Vigneau, S. et al. Homology between a 173-kb region from mouse chromosome 10, telomeric to the Ifng locus, and human chromosome 12q15. Genomics 78, 206–213 (2001).
Bernstein, B.E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).
Ansel, K.M., Djuretic, I., Tanasa, B. & Rao, A. Regulation of Th2 differentiation and Il4 locus accessibility. Annu. Rev. Immunol. 24, 607–656 (2006).
Hatton, R.D. et al. A distal conserved sequence element controls Ifng gene expression by T cells and NK cells. Immunity 25, 717–729 (2006).
Chang, S. & Aune, T.M. Histone hyperacetylated domains across the Ifng gene region in natural killer cells and T cells. Proc. Natl. Acad. Sci. USA 102, 17095–17100 (2005).
Biemont, C. & Vieira, C. Genetics: junk DNA as an evolutionary force. Nature 443, 521–524 (2006).
Xie, M.H. et al. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2–4 and IL-22R. J. Biol. Chem. 275, 31335–31339 (2000).
Liang, S.C. et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203, 2271–2279 (2006).
Koyanagi, M. et al. EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in Th1 cells. J. Biol. Chem. 280, 31470–31477 (2005).
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).
Fitzpatrick, D.R. et al. Distinct methylation of the interferon γ (IFN-γ) and interleukin 3 (IL-3) genes in newly activated primary CD8+ T lymphocytes: regional IFN-γ promoter demethylation and mRNA expression are heritable in CD44highCD8+ T cells. J. Exp. Med. 188, 103–117 (1998).