AI Article Synopsis
- - The c-fos proto-oncogene, known for its quick transcriptional activation, has been studied primarily at its canonical promoter, but important regulatory sequences have also been discovered in its first intron.
- - Researchers identified a conserved region in the c-fos first intron containing a TATA box and functional TRE and CRE sites, which enhance gene activation in fibroblasts, particularly when stimulated by calcium and cAMP.
- - Their findings suggest a new, developmentally regulated promoter in the c-fos gene, as shown by transgenic mice studies that exhibit specific LacZ expression in the developing CNS and mammary tissue.
Article Abstract
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.
Methodology/principal Findings: 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/significance: Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888593 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011235 | PLOS |
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