Binding of promoter-associated AP-1 is not altered during induction and subsequent repression of the c-jun promoter by TPA and UV irradiation.
Rapid transient induction of the human c-jun proto-oncogene by 12-O-tetradecanoylphorbol-13-acetate (TPA) and UV irradiation requires the presence of two cis-acting elements, Jun1 and Jun2. Using dimethyl sulfate (DMS) genomic footprinting, in vivo, all protein binding sites in the c-jun promoter, including Jun1 and Jun2, are already fully occupied before induction and the protein--DNA contacts are unchanged during gene activation by TPA and UV and subsequent repression. In vitro binding studies suggest that both sites are recognized with high affinity by protein complexes containing cJun and ATF-2. Jun1 is also recognized by complexes containing Fos and Jun in vitro, but with only a very low affinity. The binding of Jun/ATF-2-containing complexes to Jun1 or Jun2 is not affected during early and late time points after induction. Transcriptional shut-off is caused by neither a loss of binding of an activating protein nor by additional binding of a putative repressor. The lack of detectable changes in DNA binding and factor composition strongly suggests that transcriptional activation and subsequent inactivation of c-jun promoter activity by TPA or UV is mediated by post-translational modifications of prebound cJun and possibly ATF-2. Such pre-formed structures on the promoter could be a general requirement for the rapid and transient transcriptional responses of immediate-early genes to extracellular signals.
Herr
I
I
Kernforschungszentrum Karlsruhe, Institut für Genetik, Germany.
van Dam
H
H
Angel
P
P
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D016758:Genes, jun; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D004247:DNA; D013755:Tetradecanoylphorbol Acetate