c-Fos antagonizes the junD gene positive autoregulatory loop; a novel c-Fos role in promoter switching.
In contrast to c-jun and junB, the junD gene is constitutively expressed in quiescent cells. The junD promoter, therefore, may provide a paradigm for promoters mostly active in growth arrested cells. We report here that the human junD promoter is repressed by serum and TPA. Also, the ability of JunD to positively autoregulate its promoter is abolished under these conditions. The obtained promoter repression depends on the junD promoter TRE, suggesting the involvement of bZip proteins in this process. We found that c-Fos, a bZip protein known to be induced by serum and TPA, is sufficient to antagonize the JunD function. Furthermore, selective activation of the junD promoter by JunD is abolished by c-Fos with concomitant activation of the collagenase promoter. The latter contains a TRE that is transcriptionally activated in proliferating cells. We propose that c-Fos plays a novel role in intergenic promoter switching, downregulating quiescent-state related genes while simultaneously upregulating proliferation-state specific genes.
Berger
I
I
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Shaul
Y
Y
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D005812:Genes, Switch / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D016895:Culture Media, Serum-Free; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate