Cutting edge: the differential involvement of the N-finger of GATA-3 in chromatin remodeling and transactivation during Th2 development.
The development of Th subset is accompanied by subset-specific chromatin remodeling of cytokine gene loci. In this study, we show that the C-terminal, but not the N-terminal zinc finger (N-finger) of GATA-3 mediates the association with the IL-4/IL-13 intergenic DNase I hypersensitive site and the induction of an extended DNase I hypersensitivity on the IL-4/IL-13 locus. Consistently, deletion of the transactivation domains or the C-finger, but not the N-finger, abrogated the induction of IL-4 and IL-13 as well as the down-regulation of IFN-gamma. In contrast, the N-finger of GATA-3 was indispensable for the binding to the IL-5 promoter and the induction of IL-5. The selective use of the N-finger may underlie the differential roles of GATA-3 in the induction of IL-4, IL-13, and IL-5.
Takemoto
Naofumi
N
Department of Immunology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Arai
Ken-ichi
K
Miyatake
Shoichiro
S
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050990:GATA3 Transcription Factor; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000276:immunology*; D016335:Zinc Fingers / Q000235:genetics
D002843:Chromatin; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D015848:Interleukin-5; D015534:Trans-Activators; D015847:Interleukin-4; D004247:DNA