IL-4 ACTIVATES A LATENT DNA-BINDING FACTOR THAT BINDS A SHARED IFN-GAMMA AND IL-4 RESPONSE ELEMENT PRESENT IN THE GERM-LINE GAMMA-1 IG PROMOTER

IL-4 regulates transcription of the germ-line gamma 1 lg gene in murin e B cells and by doing so targets this isotype for switch recombinatio n by an unknown mechanism. In this study, we have identified an IL-4-i nduced DNA-binding protein factor in murine B cells designated NF-IL-4 -gamma 1. This factor binds specifically to a site within a 13-bp DNA sequence extending from -125 to -113 (5' CATTCACATGAAC 3') in the germ -line gamma 1 promoter and shown previously to be important for IL-4-r esponsive transcription. This sequence is highly homologous to the IFN -gamma activation site or GAS, and competitive binding studies demonst rate that NF-IL-4-gamma 1 can also bind to GAS elements in the promote rs of two IFN-gamma-responsive genes and to an IL-4-responsive element in the germ-line epsilon lg promoter. NF-IL-4-gamma 1 is rapidly indu ced in the absence of de novo protein synthesis and expression is sust ained through day 4 of in vitro culture with IL-4 and LPS. Induction o f NF-IL-4-gamma 1 is inhibited by the kinase inhibitor staurosporine a nd the factor itself requires phosphorylation for binding activity. Th e binding specificity and expression characteristics of NF-IL-4-gamma 1 suggest identity with other recently described IL-4-activated, GAS-b inding factors that are members of the signal transducers and activato rs of transcription (STAT) family of cytokine-responsive transcription factors.