RESUMO
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.
Assuntos
Proteínas de Ligação a DNA/farmacologia , Desoxirribonuclease I/farmacologia , Elementos Facilitadores Genéticos/imunologia , Regulação da Expressão Gênica/imunologia , Proteínas de Homeodomínio/farmacologia , Interleucina-3/genética , Proteínas Nucleares , Linfócitos T/metabolismo , Fatores de Transcrição/farmacologia , Sequência de Bases , Ciclosporina/toxicidade , Sinergismo Farmacológico , Elementos Facilitadores Genéticos/efeitos dos fármacos , Células HeLa , Fator C1 de Célula Hospedeira , Humanos , Células Jurkat , Dados de Sequência Molecular , Fatores de Transcrição NFATC , Fator 1 de Transcrição de Octâmero , Fator 2 de Transcrição de OctâmeroRESUMO
In comparing several histone H1 promoters, we have identified a highly conserved sequence element, 5'-TGTGTTA, located approx. 450-480 bp upstream from the cap site. This TG-box is a near perfect inverted repeat of the previously characterized AC-box (5'-AAACACA). The distance between these elements is also highly conserved. We performed transient transfection assays with cat gene reporter constructs which indicated that both the presence and correct position of the TG-box were essential for maximal expression of the chicken 02 H1 promoter. To the best of our knowledge, this study represents the first demonstration of an effect by the TG-box on transcription of a major histone-encoding H1 gene.