Structure and specificity of GATA proteins in Th2 development

被引:66
作者
Ranganath, S
Murphy, KM
机构
[1] Washington Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Ctr Immunol, Howard Hughes Med Inst, St Louis, MO 63110 USA
关键词
D O I
10.1128/MCB.21.8.2716-2725.2001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Development of Th2 subset of CD4(+) T cells involves the interleukin-1 (IL-4)- and Stat6-dependent increase in GATA-3 expression during primary activation. Recently we reported that the phenotypic stability and factor independence of Th2 cells involves acquisition of an intracellular pathway that maintains GATA-3 expression. Evidence from retroviral expression studies implied that this pathway involved an autoactivation of GATA-3 expression, since Stat6-deficient T cells induced endogenous GATA-3 when infected with GATA-3-expressing retroviruses. That study left unresolved the issue of whether GATA-3 autoactivation was direct or indirect. Several other Th2-specific transcription factors have been described, including c-Maf and JunB, We therefore examined the ability of these other transcription factors to induce GATA-3 expression and promote Th2 development. Neither c-Maf nor JunB induced Th2 development in Stat6-deficient CD4(+) T cells, in contrast to GATA-3, Consistent with this indication of a possible direct autoactivation pathway, we also observed that heterologous GATA family proteins GATA-1, GATA-2, and GATA-4 were also capable of inducing GATA-3 expression in developing Stat6-deficient T cells and promote Th2 development. Mutational analysis revealed evidence for two distinct mechanisms of GATA-3 action. IL-4 induction by GATA-3 required each of the functional domains to be present, whereas repression of gamma interferon could occur even when mutants of GATA-3 lacking the second transactivation domain, TA2, were expressed. The GATA-dependent induction of the GATA-3 but not the other GATA genes in T cells suggests that T-cell-specific cis elements within the GATA-3 locus likely cooperate with a general GATA recognition motif to allow GATA-3-dependent autoactivation.
引用
收藏
页码:2716 / 2725
页数:10
相关论文
共 58 条
  • [1] MOUSE GATA-4 - A RETINOIC ACID-INDUCIBLE GATA-BINDING TRANSCRIPTION FACTOR EXPRESSED IN ENDODERMALLY DERIVED TISSUES AND HEART
    ARCECI, RJ
    KING, AAJ
    SIMON, MC
    ORKIN, SH
    WILSON, DB
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (04) : 2235 - 2246
  • [2] CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation
    Blobel, GA
    Nakajima, T
    Eckner, R
    Montminy, M
    Orkin, SH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (05) : 2061 - 2066
  • [3] Regulation of activity of the transcription factor GATA-1 by acetylation
    Boyes, J
    Byfield, P
    Nakatani, Y
    Ogryzko, V
    [J]. NATURE, 1998, 396 (6711) : 594 - 598
  • [4] Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types
    Dasen, JS
    O'Connell, SM
    Flynn, SE
    Treier, M
    Gleiberman, AS
    Szeto, DP
    Hooshmand, F
    Aggarwal, AK
    Rosenfeld, MG
    [J]. CELL, 1999, 97 (05) : 587 - 598
  • [5] DORFMAN DM, 1992, J BIOL CHEM, V267, P1279
  • [6] The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors
    Durocher, D
    Charron, F
    Schwartz, RJ
    Warren, R
    Nemer, M
    [J]. EMBO JOURNAL, 1997, 16 (18) : 5687 - 5696
  • [7] Recruitment of Stat4 to the human interferon-α/β receptor requires activated Stat2
    Farrar, JD
    Smith, JD
    Murphy, TL
    Murphy, KM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (04) : 2693 - 2697
  • [8] GEORGE KM, 1994, DEVELOPMENT, V120, P2673
  • [9] A HORMONE-ENCODING GENE IDENTIFIES A PATHWAY FOR CARDIAC BUT NOT SKELETAL-MUSCLE GENE-TRANSCRIPTION
    GREPIN, C
    DAGNINO, L
    ROBITAILLE, L
    HABERSTROH, L
    ANTAKLY, T
    NEMER, M
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (05) : 3115 - 3129
  • [10] GATA ELEMENTS ARE NECESSARY FOR THE ACTIVITY AND TISSUE-SPECIFICITY OF THE T-CELL RECEPTOR BETA-CHAIN TRANSCRIPTIONAL ENHANCER
    HENDERSON, AJ
    MCDOUGALL, S
    LEIDEN, J
    CALAME, KL
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (06) : 4286 - 4294