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.