Advertisement

How Stats Interact with the Molecular Machinery of Transcriptional Activation

  • Amanda M. Jamieson
  • Matthias Farlik
  • Thomas Decker
Chapter

Abstract

The main purpose of Jak-Stat signal transduction is to adjust the fraction of genes expressed in a genome to environmental cues. The focus of this review is to summarize current knowledge and hypotheses concerning the molecular players and mechanisms that allow Stats to regulate gene expression. We pay particular attention not only to modifications of the Stats themselves, but also to interaction partners with relevance to the remodeling or modification of chromatin or to the recruitment of proteins required for transcriptional initiation and elongation.

Keywords

Interferon Regulatory Factor Variant Histone Target Promoter Stat1 Dimer S727 Phosphorylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Our work is supported by the Austrian Science fund (FWF SFB-28) and GEN-AU III (“Inflammobiota”).

References

  1. Antunes F, Marg A, Vinkemeier U (2011) STAT1 signaling is not regulated by a phosphorylation-acetylation switch. Mol Cell Biol 31:3029–3037PubMedGoogle Scholar
  2. Becker S, Groner B, Muller CW (1998) Three-dimensional structure of the Stat3beta homodimer bound to DNA. Nature 394:145–151PubMedGoogle Scholar
  3. Bennett BL, Cruz R, Lacson RG, Manning AM (1997) Interleukin-4 suppression of tumor necrosis factor alpha-stimulated E- selectin gene transcription is mediated by STAT6 antagonism of NF-kappaB. J Biol Chem 272:10212–10219PubMedGoogle Scholar
  4. Chatterjee-Kishore M, Wright KL, Ting JP, Stark GR (2000) How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene. EMBO J 19:4111–4122PubMedGoogle Scholar
  5. Chen X, Vinkemeier U, Zhao Y, Jeruzalmi D, Darnell JE Jr, Kuriyan J (1998) Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell 93:827–839PubMedGoogle Scholar
  6. Cheon H, Stark GR (2009) Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes. Proc Natl Acad Sci USA 106:9373–9378PubMedGoogle Scholar
  7. Clapier CR, Cairns BR (2009) The biology of chromatin remodeling complexes. Annu Rev Biochem 78:273–304PubMedGoogle Scholar
  8. Cuddapah S, Jothi R, Schones DE, Roh TY, Cui K, Zhao K (2009) Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res 19:24–32PubMedGoogle Scholar
  9. Cui K, Tailor P, Liu H, Chen X, Ozato K, Zhao K (2004) The chromatin-remodeling BAF complex mediates cellular antiviral activities by promoter priming. Mol Cell Biol 24:4476–4486PubMedGoogle Scholar
  10. Cvijic H, Bauer K, Loffler D, Pfeifer G, Blumert C, Kretzschmar AK, Henze C, Brocke-Heidrich K, Horn F (2009) Co-activator SRC-1 is dispensable for transcriptional control by STAT3. Biochem J 420:123–132PubMedGoogle Scholar
  11. Darnell JE Jr (1997) STATs and gene regulation. Science 277:1630–1635PubMedGoogle Scholar
  12. Darnell JE Jr, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415–1421PubMedGoogle Scholar
  13. Decker T, Kovarik P (2000) Serine phosphorylation of STATs. Oncogene 19:2628–2637PubMedGoogle Scholar
  14. Decker T, Kovarik P, Meinke A (1997) Gas elements: a few nucleotides with a major impact on cytokine-induced gene expression. J Interferon Cytokine Res 17:121–134PubMedGoogle Scholar
  15. Donnelly RP, Kotenko SV (2010) Interferon-lambda: a new addition to an old family. J Interferon Cytokine Res 30:555–564PubMedGoogle Scholar
  16. Droescher M, Begitt A, Marg A, Zacharias M, Vinkemeier U (2011) Cytokine-induced paracrystals prolong the activity of STAT transcription factors and provide a model for the regulation of protein-solubility by SUMO. J Biol Chem 286:18731–18746PubMedGoogle Scholar
  17. Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, Takahashi H, Sun HW, Kanno Y, Powrie F, O’Shea JJ (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32:605–615PubMedGoogle Scholar
  18. Elo LL, Jarvenpaa H, Tuomela S, Raghav S, Ahlfors H, Laurila K, Gupta B, Lund RJ, Tahvanainen J, Hawkins RD, Oresic M, Lahdesmaki H, Rasool O, Rao KV, Aittokallio T, Lahesmaa R (2010) Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming. Immunity 32:852–862PubMedGoogle Scholar
  19. Engblom D, Kornfeld JW, Schwake L, Tronche F, Reimann A, Beug H, Hennighausen L, Moriggl R, Schutz G (2007) Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression. Genes Dev 21:1157–1162PubMedGoogle Scholar
  20. Esashi E, Wang YH, Perng O, Qin XF, Liu YJ, Watowich SS (2008) The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity 28:509–520PubMedGoogle Scholar
  21. Farlik M, Reutterer B, Schindler C, Greten F, Vogl C, Muller M, Decker T (2010) Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression. Immunity 33:25–34PubMedGoogle Scholar
  22. Farlik M, Rapp B, Marie I, Levy DE, Jamieson AM, Decker T (2012) Contribution of a TANK-Binding Kinase 1-Interferon (IFN) Regulatory Factor 7 Pathway to IFN-γ-Induced Gene Expression. Mol Cell Biol 32:1032–1043PubMedGoogle Scholar
  23. Flammer JR, Dobrovolna J, Kennedy MA, Chinenov Y, Glass CK, Ivashkiv LB, Rogatsky I (2010) The type I interferon signaling pathway is a target for glucocorticoid inhibition. Mol Cell Biol 30:4564–4574PubMedGoogle Scholar
  24. Gewinner C, Hart G, Zachara N, Cole R, Beisenherz-Huss C, Groner B (2004) The coactivator of transcription CREB-binding protein interacts preferentially with the glycosylated form of Stat5. J Biol Chem 279:3563–3572PubMedGoogle Scholar
  25. Gil MP, Salomon R, Louten J, Biron CA (2006) Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo. Blood 107:987–993PubMedGoogle Scholar
  26. Ginsberg M, Czeko E, Muller P, Ren Z, Chen X, Darnell JE Jr (2007) Amino acid residues required for physical and cooperative transcriptional interaction of STAT3 and AP-1 proteins c-Jun and c-Fos. Mol Cell Biol 27:6300–6308PubMedGoogle Scholar
  27. Giraud S, Bienvenu F, Avril S, Gascan H, Heery DM, Coqueret O (2002) Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a. J Biol Chem 277:8004–8011PubMedGoogle Scholar
  28. Goodrich JA, Tjian R (2010) Unexpected roles for core promoter recognition factors in cell-type-specific transcription and gene regulation. Nat Rev Genet 11:549–558PubMedGoogle Scholar
  29. Gough DJ, Messina NL, Hii L, Gould JA, Sabapathy K, Robertson AP, Trapani JA, Levy DE, Hertzog PJ, Clarke CJ, Johnstone RW (2010) Functional crosstalk between type I and II interferon through the regulated expression of STAT1. PLoS Biol 8:e1000361PubMedGoogle Scholar
  30. Harada H, Matsumoto M, Sato M, Kashiwazaki Y, Kimura T, Kitagawa M, Yokochi T, Tan RS, Takasugi T, Kadokawa Y, Schindler C, Schreiber RD, Noguchi S, Taniguchi T (1996) Regulation of IFN-alpha/beta genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta. Genes Cells 1:995–1005PubMedGoogle Scholar
  31. Hargreaves DC, Horng T, Medzhitov R (2009) Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138:129–145PubMedGoogle Scholar
  32. Hartman SE, Bertone P, Nath AK, Royce TE, Gerstein M, Weissman S, Snyder M (2005) Global changes in STAT target selection and transcription regulation upon interferon treatments. Genes Dev 19:2953–2968PubMedGoogle Scholar
  33. Hertzog PJ, O’Neill LA, Hamilton JA (2003) The interferon in TLR signaling: more than just antiviral. Trends Immunol 24:534–539PubMedGoogle Scholar
  34. Horvai AE, Xu L, Korzus E, Brard G, Kalafus D, Mullen TM, Rose DW, Rosenfeld MG, Glass CK (1997) Nuclear integration of jak/stat and ras/ap 1 signaling by cbp and p300. Proc Natl Acad Sci USA 94:1074–1079PubMedGoogle Scholar
  35. Horvath CM, Stark GR, Kerr IM, Darnell JE Jr (1996) Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex. Mol Cell Biol 16:6957–6964PubMedGoogle Scholar
  36. Huang M, Qian F, Hu Y, Ang C, Li Z, Wen Z (2002) Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-alpha-inducible genes. Nat Cell Biol 4:774–781PubMedGoogle Scholar
  37. Kamijo R, Harada H, Matsuyama T, Bosland M, Gerecitano J, Shapiro D, Le J, Koh SI, Kimura T, Green SJ et al (1994) Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 263:1612–1615PubMedGoogle Scholar
  38. Kanno Y, Levi BZ, Tamura T, Ozato K (2005) Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex. J Interferon Cytokine Res 25:770–779PubMedGoogle Scholar
  39. Kim YJ, Bjorklund S, Li Y, Sayre MH, Kornberg RD (1994) A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 77:599–608PubMedGoogle Scholar
  40. Kramer OH, Knauer SK, Greiner G, Jandt E, Reichardt S, Guhrs KH, Stauber RH, Bohmer FD, Heinzel T (2009) A phosphorylation-acetylation switch regulates STAT1 signaling. Genes Dev 23:223–235PubMedGoogle Scholar
  41. Kumar A, Commane M, Flickinger TW, Horvath CM, Stark GR (1997) Defective TNF-alpha-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases. Science 278:1630–1632PubMedGoogle Scholar
  42. Kurokawa R, Kalafus D, Ogliastro MH, Kioussi C, Xu L, Torchia J, Rosenfeld MG, Glass CK (1998) Differential use of CREB binding protein-coactivator complexes. Science 279:700–703PubMedGoogle Scholar
  43. Kwon MC, Koo BK, Moon JS, Kim YY, Park KC, Kim NS, Kwon MY, Kong MP, Yoon KJ, Im SK, Ghim J, Han YM, Jang SK, Shong M, Kong YY (2008a) Crif1 is a novel transcriptional coactivator of STAT3. EMBO J 27:642–653PubMedGoogle Scholar
  44. Kwon SY, Xiao H, Glover BP, Tjian R, Wu C, Badenhorst P (2008b) The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila innate immunity. Dev Biol 316:538–547PubMedGoogle Scholar
  45. Kwon H, Thierry-Mieg D, Thierry-Mieg J, Kim HP, Oh J, Tunyaplin C, Carotta S, Donovan CE, Goldman ML, Tailor P, Ozato K, Levy DE, Nutt SL, Calame K, Leonard WJ (2009) Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors. Immunity 31:941–952PubMedGoogle Scholar
  46. Lau JF, Nusinzon I, Burakov D, Freedman LP, Horvath CM (2003) Role of metazoan mediator proteins in interferon-responsive transcription. Mol Cell Biol 23:620–628PubMedGoogle Scholar
  47. Lerner L, Henriksen MA, Zhang X, Darnell JE Jr (2003) STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene. Genes Dev 17:2564–2577PubMedGoogle Scholar
  48. Letimier FA, Passini N, Gasparian S, Bianchi E, Rogge L (2007) Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rbeta2 expression during human Th1 cell differentiation. EMBO J 26:1292–1302PubMedGoogle Scholar
  49. Leverson JD, Koskinen PJ, Orrico FC, Rainio EM, Jalkanen KJ, Dash AB, Eisenman RN, Ness SA (1998) Pim-1 kinase and p100 cooperate to enhance c-Myb activity. Mol Cell 2:417–425PubMedGoogle Scholar
  50. Levy DE, Darnell JE Jr (2002) Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3:651–662PubMedGoogle Scholar
  51. Levy DE, Kessler DS, Pine R, Reich N, Darnell JE Jr (1988) Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Dev 2:383–393PubMedGoogle Scholar
  52. Litterst CM, Pfitzner E (2001) Transcriptional activation by STAT6 requires the direct interaction with NCoA-1. J Biol Chem 276:45713–45721PubMedGoogle Scholar
  53. Litterst CM, Kliem S, Marilley D, Pfitzner E (2003) NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the alpha-helical region of the STAT5 transactivation domain. J Biol Chem 278:45340–45351PubMedGoogle Scholar
  54. Liu H, Kang H, Liu R, Chen X, Zhao K (2002) Maximal induction of a subset of interferon target genes requires the chromatin-remodeling activity of the BAF complex. Mol Cell Biol 22:6471–6479PubMedGoogle Scholar
  55. Longman RS, Braun D, Pellegrini S, Rice CM, Darnell RB, Albert ML (2007) Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-alpha/beta on antigen cross-presentation. Blood 109:1113–1122PubMedGoogle Scholar
  56. Macquarrie KL, Fong AP, Morse RH, Tapscott SJ (2011) Genome-wide transcription factor binding: beyond direct target regulation. Trends Genet 27:141–148PubMedGoogle Scholar
  57. Maldonado RA, Soriano MA, Perdomo LC, Sigrist K, Irvine DJ, Decker T, Glimcher LH (2009) Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse. J Exp Med 206:877–892PubMedGoogle Scholar
  58. Malik S, Roeder RG (2010) The metazoan mediator co-activator complex as an integrative hub for transcriptional regulation. Nat Rev Genet 11:761–772PubMedGoogle Scholar
  59. Mao X, Ren Z, Parker GN, Sondermann H, Pastorello MA, Wang W, McMurray JS, Demeler B, Darnell JE Jr, Chen X (2005) Structural bases of unphosphorylated STAT1 association and receptor binding. Mol Cell 17:761–771PubMedGoogle Scholar
  60. Maritano D, Sugrue ML, Tininini S, Dewilde S, Strobl B, Fu X, Murray-Tait V, Chiarle R, Poli V (2004) The STAT3 isoforms alpha and beta have unique and specific functions. Nat Immunol 5:401–409PubMedGoogle Scholar
  61. Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, Kundig TM, Amakawa R, Kishihara K, Wakeham A, Potter J, Furlonger LC, Narendran A, Suzuki H, Ohashi PS, Paige CJ, Taniguchi T, Mak TW (1993) Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell 75:83–97PubMedGoogle Scholar
  62. Meissner T, Krause E, Lodige I, Vinkemeier U (2004) Arginine methylation of STAT1: a reassessment. Cell 119:587–589, discussion 589–590PubMedGoogle Scholar
  63. Mertens C, Zhong M, Krishnaraj R, Zou W, Chen X, Darnell JE Jr (2006) Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain. Genes Dev 20:3372–3381PubMedGoogle Scholar
  64. Miyagi T, Gil MP, Wang X, Louten J, Chu WM, Biron CA (2007) High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells. J Exp Med 204:2383–2396PubMedGoogle Scholar
  65. Mo C, Chearwae W, O’Malley JT, Adams SM, Kanakasabai S, Walline CC, Stritesky GL, Good SR, Perumal NB, Kaplan MH, Bright JJ (2008) Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis. J Immunol 181:5681–5690PubMedGoogle Scholar
  66. Moriggl R, Sexl V, Kenner L, Duntsch C, Stangl K, Gingras S, Hoffmeyer A, Bauer A, Piekorz R, Wang DM, Bunting KD, Wagner EF, Sonneck K, Valent P, Ihle JN, Beug H (2005) Stat5 tetramer formation is associated with leukemogenesis. Cancer Cell 7:87–99PubMedGoogle Scholar
  67. Morris AC, Beresford GW, Mooney MR, Boss JM (2002) Kinetics of a gamma interferon response: expression and assembly of CIITA promoter IV and inhibition by methylation. Mol Cell Biol 22:4781–4791PubMedGoogle Scholar
  68. Mowen KA, Tang J, Zhu W, Schurter BT, Shuai K, Herschman HR, David M (2001) Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription. Cell 104:731–741PubMedGoogle Scholar
  69. Muhlethaler-Mottet A, Di Berardino W, Otten LA, Mach B (1998) Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Immunity 8:157–166PubMedGoogle Scholar
  70. Nakajima H, Brindle PK, Handa M, Ihle JN (2001) Functional interaction of STAT5 and nuclear receptor co-repressor SMRT: implications in negative regulation of STAT5-dependent transcription. EMBO J 20:6836–6844PubMedGoogle Scholar
  71. Nakashima K, Yanagisawa M, Arakawa H, Kimura N, Hisatsune T, Kawabata M, Miyazono K, Taga T (1999) Synergistic signaling in fetal brain by STAT3-smad1 complex bridged by p300. Science 284:479–482PubMedGoogle Scholar
  72. Neculai D, Neculai AM, Verrier S, Straub K, Klumpp K, Pfitzner E, Becker S (2005) Structure of the unphosphorylated STAT5a dimer. J Biol Chem 280:40782–40787PubMedGoogle Scholar
  73. Ni Z, Bremner R (2007) Brahma-related gene 1-dependent STAT3 recruitment at IL-6-inducible genes. J Immunol 178:345–351PubMedGoogle Scholar
  74. Ni Z, Karaskov E, Yu T, Callaghan SM, Der S, Park DS, Xu Z, Pattenden SG, Bremner R (2005) Apical role for BRG1 in cytokine-induced promoter assembly. Proc Natl Acad Sci USA 102:14611–14616PubMedGoogle Scholar
  75. Ni Z, Abou El Hassan M, Xu Z, Yu T, Bremner R (2008) The chromatin-remodeling enzyme BRG1 coordinates CIITA induction through many interdependent distal enhancers. Nat Immunol 9:785–793PubMedGoogle Scholar
  76. Nusinzon I, Horvath CM (2005) Unexpected roles for deacetylation in interferon- and cytokine-induced transcription. J Interferon Cytokine Res 25:745–748PubMedGoogle Scholar
  77. O’Shea JJ, Lahesmaa R, Vahedi G, Laurence A, Kanno Y (2011) Genomic views of STAT function in CD4(+) T helper cell differentiation. Nat Rev Immunol 11:239–250PubMedGoogle Scholar
  78. Ohmori Y, Hamilton TA (1997) IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages. J Immunol 159:5474–5482PubMedGoogle Scholar
  79. Onodera A, Yamashita M, Endo Y, Kuwahara M, Tofukuji S, Hosokawa H, Kanai A, Suzuki Y, Nakayama T (2010) STAT6-mediated displacement of polycomb by trithorax complex establishes long-term maintenance of GATA3 expression in T helper type 2 cells. J Exp Med 207:2493–2506PubMedGoogle Scholar
  80. Ouchi T, Lee SW, Ouchi M, Aaronson SA, Horvath CM (2000) Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes. Proc Natl Acad Sci USA 97:5208–5213PubMedGoogle Scholar
  81. Ozsolak F, Milos PM (2010) RNA sequencing: advances, challenges and opportunities. Nat Rev Genet 12:87–98PubMedGoogle Scholar
  82. Park C, Li S, Cha E, Schindler C (2000) Immune response in Stat2 knockout mice. Immunity 13:795–804PubMedGoogle Scholar
  83. Pattenden SG, Klose R, Karaskov E, Bremner R (2002) Interferon-gamma-induced chromatin remodeling at the CIITA locus is BRG1 dependent. EMBO J 21:1978–1986PubMedGoogle Scholar
  84. Paukku K, Yang J, Silvennoinen O (2003) Tudor and nuclease-like domains containing protein p100 function as coactivators for signal transducer and activator of transcription 5. Mol Endocrinol 17:1805–1814PubMedGoogle Scholar
  85. Paulson M, Pisharody S, Pan L, Guadagno S, Mui AL, Levy DE (1999) Stat protein transactivation domains recruit p300/CBP through widely divergent sequences. J Biol Chem 274:25343–25349PubMedGoogle Scholar
  86. Paulson M, Press C, Smith E, Tanese N, Levy DE (2002) IFN-stimulated transcription through a TBP-free acetyltransferase complex escapes viral shutoff. Nat Cell Biol 4:140–147PubMedGoogle Scholar
  87. Pine R, Canova A, Schindler C (1994) Tyrosine phosphorylated p91 binds to a single element in the ISGF2/IRF-1 promoter to mediate induction by IFN alpha and IFN gamma, and is likely to autoregulate the p91 gene. EMBO J 13:158–167PubMedGoogle Scholar
  88. Ramana CV, Gil MP, Han Y, Ransohoff RM, Schreiber RD, Stark GR (2001) Stat1-independent regulation of gene expression in response to IFN-gamma. Proc Natl Acad Sci USA 98:6674–6679PubMedGoogle Scholar
  89. Ramirez-Carrozzi VR, Braas D, Bhatt DM, Cheng CS, Hong C, Doty KR, Black JC, Hoffmann A, Carey M, Smale ST (2009) A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell 138:114–128PubMedGoogle Scholar
  90. Ramsauer K, Farlik M, Zupkovitz G, Seiser C, Kroger A, Hauser H, Decker T (2007) Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. Proc Natl Acad Sci USA 104:2849–2854PubMedGoogle Scholar
  91. Rascle A, Johnston JA, Amati B (2003) Deacetylase activity is required for recruitment of the basal transcription machinery and transactivation by STAT5. Mol Cell Biol 23:4162–4173PubMedGoogle Scholar
  92. Razeto A, Ramakrishnan V, Litterst CM, Giller K, Griesinger C, Carlomagno T, Lakomek N, Heimburg T, Lodrini M, Pfitzner E, Becker S (2004) Structure of the NCoA-1/SRC-1 PAS-B domain bound to the LXXLL motif of the STAT6 transactivation domain. J Mol Biol 336:319–329PubMedGoogle Scholar
  93. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79–82PubMedGoogle Scholar
  94. Robertson AG, Bilenky M, Tam A, Zhao Y, Zeng T, Thiessen N, Cezard T, Fejes AP, Wederell ED, Cullum R, Euskirchen G, Krzywinski M, Birol I, Snyder M, Hoodless PA, Hirst M, Marra MA, Jones SJ (2008) Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding. Genome Res 18:1906–1917PubMedGoogle Scholar
  95. Sadzak I, Schiff M, Gattermeier I, Glinitzer R, Sauer I, Saalmuller A, Yang E, Schaljo B, Kovarik P (2008) Recruitment of Stat1 to chromatin is required for interferon-induced serine phosphorylation of Stat1 transactivation domain. Proc Natl Acad Sci USA 105:8944–8949PubMedGoogle Scholar
  96. Schaefer TS, Sanders LK, Nathans D (1995) Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proc Natl Acad Sci USA 92:9097–9101PubMedGoogle Scholar
  97. Schindler C, Levy DE, Decker T (2007) JAK-STAT signaling: from interferons to cytokines. J Biol Chem 282:20059–20063PubMedGoogle Scholar
  98. Shen Y, Schlessinger K, Zhu X, Meffre E, Quimby F, Levy DE, Darnell JE Jr (2004) Essential role of STAT3 in postnatal survival and growth revealed by mice lacking STAT3 serine 727 phosphorylation. Mol Cell Biol 24:407–419PubMedGoogle Scholar
  99. Shi S, Calhoun HC, Xia F, Li J, Le L, Li WX (2006) JAK signaling globally counteracts heterochromatic gene silencing. Nat Genet 38:1071–1076PubMedGoogle Scholar
  100. Shi M, Lin TH, Appell KC, Berg LJ (2008a) Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. Immunity 28:763–773PubMedGoogle Scholar
  101. Shi S, Larson K, Guo D, Lim SJ, Dutta P, Yan SJ, Li WX (2008b) Drosophila STAT is required for directly maintaining HP1 localization and heterochromatin stability. Nat Cell Biol 10:489–496PubMedGoogle Scholar
  102. Stark GR (2007) How cells respond to interferons revisited: from early history to current complexity. Cytokine Growth Factor Rev 18:419–423PubMedGoogle Scholar
  103. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264PubMedGoogle Scholar
  104. Stocklin E, Wissler M, Gouilleux F, Groner B (1996) Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383:726–728, ISSN: 0028-0836PubMedGoogle Scholar
  105. Sun W, Xu W, Snyder M, He W, Ho H, Ivashkiv LB, Zhang JJ (2005) The conserved Leu-724 residue is required for both serine phosphorylation and co-activator recruitment for Stat1-mediated transcription activation in response to interferon-gamma. J Biol Chem 280:41844–41851PubMedGoogle Scholar
  106. Szanto A, Balint BL, Nagy ZS, Barta E, Dezso B, Pap A, Szeles L, Poliska S, Oros M, Evans RM, Barak Y, Schwabe J, Nagy L (2010) STAT6 transcription factor is a facilitator of the nuclear receptor PPARgamma-regulated gene expression in macrophages and dendritic cells. Immunity 33:699–712PubMedGoogle Scholar
  107. Tamura T, Smith M, Kanno T, Dasenbrock H, Nishiyama A, Ozato K (2009) Inducible deposition of the histone variant H3.3 in interferon-stimulated genes. J Biol Chem 284:12217–12225PubMedGoogle Scholar
  108. Tenoever BR, Ng SL, Chua MA, McWhirter SM, Garcia-Sastre A, Maniatis T (2007) Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. Science 315:1274–1278PubMedGoogle Scholar
  109. Ungureanu D, Vanhatupa S, Gronholm J, Palvimo JJ, Silvennoinen O (2005) SUMO-1 conjugation selectively modulates STAT1-mediated gene responses. Blood 106:224–226PubMedGoogle Scholar
  110. Valouev A, Johnson DS, Sundquist A, Medina C, Anton E, Batzoglou S, Myers RM, Sidow A (2008) Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data. Nat Methods 5:829–834PubMedGoogle Scholar
  111. Varinou L, Ramsauer K, Karaghiosoff M, Kolbe T, Pfeffer K, Muller M, Decker T (2003) Phosphorylation of the Stat1 transactivation domain is required for full-fledged IFN-gamma-dependent innate immunity. Immunity 19:793–802PubMedGoogle Scholar
  112. Vinkemeier U, Cohen SL, Moarefi I, Chait BT, Kuriyan J, Darnell JE Jr (1996) DNA binding of in vitro activated Stat1 alpha, Stat1 beta and truncated Stat1: interaction between NH2-terminal domains stabilizes binding of two dimers to tandem DNA sites. EMBO J 15:5616–5626PubMedGoogle Scholar
  113. Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, Cui K, Kanno Y, Roh TY, Watford WT, Schones DE, Peng W, Sun HW, Paul WE, O'Shea JJ, Zhao K (2009) Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30(1):155–167Google Scholar
  114. Wei L, Vahedi G, Sun HW, Watford WT, Takatori H, Ramos HL, Takahashi H, Liang J, Gutierrez-Cruz G, Zang C, Peng W, O’Shea JJ, Kanno Y (2010) Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity 32:840–851PubMedGoogle Scholar
  115. Wojciak JM, Martinez-Yamout MA, Dyson HJ, Wright PE (2009) Structural basis for recruitment of CBP/p300 coactivators by STAT1 and STAT2 transactivation domains. EMBO J 28:948–958PubMedGoogle Scholar
  116. Wormald S, Hilton DJ, Smyth GK, Speed TP (2006) Proximal genomic localization of STAT1 binding and regulated transcriptional activity. BMC Genomics 7:254PubMedGoogle Scholar
  117. Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S, Berkofsky-Fessler W, McConnell MJ, Pandolfi PP, Licht JD, Williams BR (2009) Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity 30:802–816PubMedGoogle Scholar
  118. Yan Z, Cui K, Murray DM, Ling C, Xue Y, Gerstein A, Parsons R, Zhao K, Wang W (2005) PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes. Genes Dev 19:1662–1667PubMedGoogle Scholar
  119. Yang J, Aittomaki S, Pesu M, Carter K, Saarinen J, Kalkkinen N, Kieff E, Silvennoinen O (2002) Identification of p100 as a coactivator for STAT6 that bridges STAT6 with RNA polymerase II. EMBO J 21:4950–4958PubMedGoogle Scholar
  120. Yang J, Chatterjee-Kishore M, Staugaitis SM, Nguyen H, Schlessinger K, Levy DE, Stark GR (2005) Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res 65:939–947PubMedGoogle Scholar
  121. Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR (2007) Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev 21:1396–1408PubMedGoogle Scholar
  122. Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, Chance MR, Chen X, Du Y, Wang Y, An L, Wang Q, Lu T, Zhang X, Wang Z, Stark GR (2010) Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc Natl Acad Sci USA 107:21499–21504PubMedGoogle Scholar
  123. York B, O’Malley BW (2010) Steroid receptor coactivator (SRC) family: masters of systems biology. J Biol Chem 285:38743–38750PubMedGoogle Scholar
  124. Zakharova N, Lymar ES, Yang E, Zhang JJ, Roeder RG, Darnell JE Jr (2003) Distinct transcriptional activation functions of STAT1alpha and beta on DNA and chromatin templates. J Biol Chem 278:43067–43073PubMedGoogle Scholar
  125. Zhang X, Darnell JE Jr (2001) Functional importance of Stat3 tetramerization in activation of the alpha 2-macroglobulin gene. J Biol Chem 276:33576–33581PubMedGoogle Scholar
  126. Zhang JJ, Vinkemeier U, Gu W, Chakravarti D, Horvath CM, Darnell JE Jr (1996) Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling. Proc Natl Acad Sci USA 93:15092–15096PubMedGoogle Scholar
  127. Zhang JJ, Zhao Y, Chait BT, Lathem WW, Ritzi M, Knippers R, Darnell JE Jr (1998) Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation. EMBO J 17:6963–6971PubMedGoogle Scholar
  128. Zhong M, Henriksen MA, Takeuchi K, Schaefer O, Liu B, ten Hoeve J, Ren Z, Mao X, Chen X, Shuai K, Darnell JE Jr (2005) Implications of an antiparallel dimeric structure of nonphosphorylated STAT1 for the activation-inactivation cycle. Proc Natl Acad Sci USA 102:3966–3971PubMedGoogle Scholar
  129. Zhu M-h, John S, Berg M, Leonard WJ (1999) Functional association of Nmi with Stat5 and Stat1 in IL-2 and IFN-γ-mediated signaling. Cell 96:121–130PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  • Amanda M. Jamieson
    • 1
  • Matthias Farlik
    • 1
  • Thomas Decker
    • 1
  1. 1.Department of Microbiology, Immunobiology and Genetics, Max F. Perutz LaboratoriesUniversity of ViennaViennaAustria

Personalised recommendations