A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site.
Interleukin-3 (IL-3) is a cytokine that is expressed primarily in activated T cells. Here we identified an inducible T cell-specific enhancer 14 kb upstream of the IL-3 gene that responded to activation of T cell receptor signaling pathways. The IL-3 enhancer spanned an inducible cyclosporin A-sensitive DNase I-hypersensitive site found only in T cells. Four NFAT-like elements exist within the enhancer. The two most active NFAT-like elements were located at the center of the DNase I-hypersensitive site. One of these NFAT-like elements encompassed overlapping Oct- and NFATp/c-binding sites, which functioned in a highly synergistic manner. We suggest that the T cell-specific expression of the IL-3 gene is partly controlled through the enhancer by cooperation between Oct and NFAT family proteins.
Duncliffe
K N
KN
Division of Human Immunology, Hanson Centre For Cancer Research, Institute for Medical and Veterinary Science, Adelaide, Australia.
Bert
A G
AG
Vadas
M A
MA
Cockerill
P N
PN
D001483:Base Sequence; D016572:Cyclosporine / Q000633:toxicity; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D003850:Deoxyribonuclease I / Q000494:pharmacology*; D004357:Drug Synergism; D004742:Enhancer Elements, Genetic / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000494:pharmacology*; D051863:Host Cell Factor C1; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics*; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000494:pharmacology*
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D007377:Interleukin-3; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C494165:POU2F1 protein, human; C058435:POU2F2 protein, human; D014157:Transcription Factors; D016572:Cyclosporine; D003850:Deoxyribonuclease I