The role of putative intragenic control elements in c-fos regulation by calcium and growth factor signalling pathways.
Sequences in the transcribed region of the c-fos gene have been suggested to control c-fos induction following exposure of cells to mitogens or stimuli that increase intracellular calcium concentrations. Using a mutational analysis we show that putative regulatory elements present in the first intron of the human c-fos gene and the fos-intragenic-regulatory-element (FIRE) are not required for c-fos regulation by growth factor and calcium signalling pathways in AtT20 and PC12 cells. Removal of the c-fos first intron and the FIRE did not increase the basal level of c-fos mRNA and only moderately reduced the magnitude of calcium-induced transcription mediated by either the entire c-fos promoter or the cAMP response element (CRE). Intragenic mutations did not affect serum response element (SRE)-dependent gene expression induced by calcium signals but caused a superinduction of c-fos expression in nerve growth factor-stimulated PC12 cells. These results indicate that c-fos promoter elements, rather than intragenic sequences, are the principal targets of transcription-regulating signalling pathways. This suggests that CRE- and SRE-bound activators of transcription initiation may also enhance, in a signal-dependent manner, c-fos transcript elongation beyond promoter-proximal pause sites.
Lange
C M
CM
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
Bading
H
H
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D016762:Genes, fos / Q000235:genetics*; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation / Q000235:genetics; D023282:Nuclease Protection Assays; D016716:PC12 Cells; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
D006133:Growth Substances; D012333:RNA, Messenger; D002118:Calcium