Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells.
The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3-dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3-dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development.
Zhou
M
M
Department of Pathology and Immunology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Ouyang
W
W
Gong
Q
Q
Katz
S G
SG
White
J M
JM
Orkin
S H
SH
Murphy
K M
KM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D050990:GATA3 Transcription Factor; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000502:physiology*; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D009687:Nuclear Proteins; C499308:Rag2 protein, mouse; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; C498432:ZFPM1 protein, human; C107310:Zfpm1 protein, mouse; D015847:Interleukin-4