A novel mouse c-fos intronic promoter that responds to CREB and AP-1 is developmentally regulated in vivo.
BACKGROUND
The c-fos proto-oncogene is an archetype for rapid and integrative transcriptional activation. Innumerable studies have focused on the canonical promoter, located upstream from the transcriptional start site. However, several regulatory sequences have been found in the first intron.


RESULTS
Here we describe an extremely conserved region in c-fos first intron that contains a putative TATA box, and functional TRE and CRE sites. This fragment drives reporter gene activation in fibroblasts, which is enhanced by increasing intracellular calcium and cAMP and by cotransfection of CREB or c-Fos/c-Jun expression vectors. We produced transgenic mice expressing a lacZ reporter controlled by the intronic promoter. Lac Z expression of this promoter is restricted to the developing central nervous system (CNS) and the mesenchyme of developing mammary buds in embryos 12.5 days post-conception, and to brain tissue in adults. RT-QPCR analysis of tissue mRNA, including the anlage of the mammary gland and the CNS, confirms the existence of a novel, nested mRNA initiated in the first intron.


CONCLUSIONS
Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene.
Coulon
Vincent
V
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, Université Montpellier 2, Université Montpellier 1, Montpellier, France. vincent.coulon@igmm.cnrs.fr
Chebli
Karim
K
Cavelier
Patricia
P
Blanchard
Jean-Marie
JM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D019143:Evolution, Molecular; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007438:Introns / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016385:TATA Box / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014981:Xenopus; D001616:beta-Galactosidase / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D008156:Luciferases; D001616:beta-Galactosidase