Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo.
By DNase I hypersensitivity analysis, we have identified an inducible, cyclosporin A-sensitive enhancer located 3' of the interleukin-4 (IL-4) gene. The enhancer binds the Th2-specific transcription factor GATA3 in vivo but is not perceptibly influenced by the absence of a second Th2-specific factor, cMaf. The antigen-inducible transcription factor NFAT1 binds the IL-4 enhancer and the IL-4 promoter only in stimulated Th2 cells; conversely, NFAT1 binds to the interferon (IFN)-gamma promoter only in stimulated Th1 cells. Our results support a model whereby transcription factors such as NFAT1, which are nonselectively induced in antigen-stimulated T cells, gain access to cytokine regulatory regions only in the appropriate subset of differentiated T cells in vivo. This restricted access enables antigen-dependent and subset-specific transcription of cytokine genes.
Agarwal
S
S
Department of Pathology, Harvard Medical School and the Center for Blood Research, Boston, Massachusetts 02115, USA.
Avni
O
O
Rao
A
A
D020413:3' Untranslated Regions / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000187:drug effects / Q000276:immunology*; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051257:Proto-Oncogene Proteins c-maf; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D020413:3' Untranslated Regions; D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C495608:Maf protein, mouse; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D016572:Cyclosporine; D003850:Deoxyribonuclease I