FUNCTIONAL-ROLE AND SIGNAL-INDUCED MODULATION OF PROTEINS RECOGNIZINGTHE CONSERVED TCATTT-CONTAINING PROMOTER ELEMENTS IN THE MURINE IL-5 AND GM-CSF GENES IN T-LYMPHOCYTES

The TCATTT-containing element extending from -61 to -41 of the mouse I L-5 gene is highly conserved in the corresponding region of the granul ocyte-macrophage colony-stimulating factor (GM-CSF) gene and has been previously shown to be involved in regulating inducible GM-CSF gene ex pression. By using stable transfection assays in the mouse Th2 clone D 10.G4.1, we show that the TCATTT-containing element is also involved i n the regulation of inducible IL-5 gene expression. The mouse IL-5 and CM-CSF homologues of this element were found by gel shift analysis to form DNA-nuclear protein complexes of similar electrophoretic mobilit y under conditions in which expression of these genes is induced. Howe ver, comparative studies using extracts of D10.G4.1 cells treated with the cellular activators Con A and PMA and the inhibitors cycloheximid e and cyclosporin A indicated that the binding activities to the conse rved elements in the IL-5 and GM-CSF genes (designated NF-IL-5A and NF -GM-CSFA, respectively) are regulated by different signaling pathways. In addition, NF-IL-5A is not induced in the Th1 clone HDK-1 which doe s not express the IL-5 gene. The strong correlation between the signal -dependent and cell-specific modulation of IL-5 and GM-CSF gene expres sion patterns and the binding activities of NF-IL-5A and NF-GM-CSFA su ggests that these nuclear proteins are involved in the transduction of T cell activation signals to the transcriptional machinery of these g enes through their interactions with their respective TCATTT-containin g elements.