trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation

Fos protein can trans-activate AP-1-dependent gene expression and trans-repress the c-fos promoter. Although we find that trans-repression is enhanced by coexpression of c-Jun, it does not require any of the AP-1 or ATF sites in the mouse c-fos promoter. A major target for repression is the serum response element (SRE). Fos mutants with an impaired leucine zipper are defective in trans-repression and transformation, suggesting that these functions involve the formation of Fos protein complexes. In contrast, mutations that abolish DNA binding of Fos enhance trans-repression but destroy the transforming potential of Fos. In addition, v-Fos protein efficiently transforms but is unable to trans-repress. These findings point to different mechanisms involved in trans-activation and trans-repression and suggest that trans-repression of the type described here is neither sufficient nor required for Fos-induced transformation.     

DNA binding activities of three murine Jun proteins: stimulation by Fos

Three members of the Jun/AP-1 family have been identified in mouse cDNA libraries: c-Jun, Jun-B, and Jun-D. We have compared the DNA binding properties of the Jun proteins by using in vitro translation products in gel retardation assays. Each protein was able to bind to the consensus AP-1 site (TGACTCA) and, with lower affinity, to related sequences, including the cyclic AMP response element TGACGTCA. The relative binding to the oligonucleotides tested was similar for the different proteins. The Jun proteins formed homodimers and heterodimers with other members of the family, and they were bound to the AP-1 site as dimers. When Fos translation product was present, DNA binding by Jun increased markedly, and the DNA complex contained Fos. The C-terminal homology region of Jun was sufficient for DNA binding, dimer formation, and interaction with Fos. Our general conclusion is that c-Jun, Jun-B, and Jun-D are similar in their DNA binding properties and in their interaction with Fos. If there are functional differences between them, they are likely to involve other activities of the Jun proteins.