GROWTH-HORMONE AND COLONY-STIMULATING FACTOR-1 SHARE MULTIPLE RESPONSE ELEMENTS IN THE C-FOS PROMOTER

The c-fos protooncogene is induced by GH rapidly, but transiently. Induction requires C kinase activation and the serum response element, and recent binding studies have also implicated the sis-inducible element (SIE). However, no systematic study of the promoter elements responsible for transactivation by GH has been undertaken. Here we used Chinese hamster ovary K1 cells transiently cotransfected with rabbit GH receptor and c-fos promoter-luciferase constructs to demonstrate that the major region responsible for GH induction is located between 284-396 base pairs upstream of the transcription start site. Full induction by GK requires all of the known elements located in this region to be intact, including the SIE or signal transducer and activator of transcription binding element. We also report novel negative elements located around -216 upstream of the start site that reduce induction by GH and provide gel shift evidence for factors binding in this region. Cotransfection of Chinese hamster ovary K1 cells with c-fms and c-fos promoter constructs followed by the addition of CSF-1 revealed that these same c-fos elements contribute to transactivation by c-fms. Serum also uses the same elements to induce c-fos expression, except for the SIE. These results indicate that GH receptor and c-fms tyrosine kinase operate through multiple common response elements to regulate c-fos gene expression despite their structural differences.