title: Essential contribution of intron sequences to Ca(2+)-dependent activation of c-fos transcription in pituitary cells.
abstract: In pituitary cells, c-fos transcription induced by releasing hormones and growth factors results from enhanced initiation of transcription, and sustained elongation of transcripts beyond the first intron. We studied the regulatory role of the first intron of the mouse c-fos gene for the control of its transcription in rat pituitary cells. We showed that the intron contains a block to elongation which is relieved by physiological activators TRH and EGF. By expressing luciferase under the control of the c-fos promoter including the first intron in reporter gene constructs, we demonstrate enhancement of TRH and EGF transcriptional stimulation by intron sequences. Further analysis of Ca(2+) signalling-depending transcription showed that the intron contains control elements in addition to the block to elongation, and that sequences in the first intron can mediate Ca(2+)-stimulated transcription also with a minimal or the SV40 promoter, irrespective of the presence or absence of the intronic block site. Within the c-fos promoter the serum response element and the cAMP response element play a permissive role in Ca(2+)- and cAMP-enhanced transcription of intron containing reporter genes. Specific binding of nuclear proteins to a consensus enhancer binding site (Sp1) within the first intron of c-fos was demonstrated, which might reflect one of the mechanisms that link Ca(2+) and intron sequences to c-fos expression. These findings point towards important functions of intronic sequences in gene transcription control.
authors.affiliation: Fondation pour Recherches Médicales, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: van Haasteren
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Ryser
authors.forename: W
authors.initials: W
authors.lastname: Schlegel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000502:physiology*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D010902:Pituitary Gland / Q000166:cytology* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D013973:Thyrotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D011189:Potassium Chloride; D000242:Cyclic AMP; D008156:Luciferases; D002118:Calcium