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A unique bFGF-responsive transcriptional element
M A Mohideen1, A Hruska-Hageman, M Nilsen-Hamilton
1Department of Biochemistry and Biophysics and the Molecular, Cellular, Iowa State University, Ames 50011, USA.
Abstract:
The mitogen-regulated protein/proliferin (mrp/plf) genes encode closely related proteins that stimulate cell proliferation and angiogenesis. Basic fibroblast growth factor (bFGF) increases mrp/plf mRNA and protein production by 3T3 cells. Although the three cloned mrp/plf gene promoters are over 97% identical, only mrp3 is transcriptionally activated by bFGF. A series of truncated mrp3 promoter sequences were tested to determine the minimal promoter sequence necessary for bFGF-responsive transcription. Within the minimal bFGF-responsive mrp3 promoter fragment, a putative FGF-regulatory element (FRE) was identified. Nuclear factors that bind the FRE are present in 3T3 cells. When present upstream of a thymidine kinase basal promoter, the FRE exhibits high transcriptional activity and responds to bFGF. Thus, the FRE is a strong transcriptional element that is regulated by bFGF and that may participate in regulating the mrp3 gene and perhaps other FGF-regulated genes.
Insights
Basic fibroblast growth factor (bFGF) activates mrp3 gene transcription via a novel FGF-regulatory element (FRE). This element, identified in 3T3 cells, drives bFGF-responsive gene expression, suggesting a role in regulating mrp3 and other FGF-target genes.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Mitogen-regulated protein/proliferin (mrp/plf) genes encode proteins involved in cell proliferation and angiogenesis.
- Basic fibroblast growth factor (bFGF) stimulates mrp/plf mRNA and protein production in 3T3 cells.
Purpose of the Study:
- To identify the minimal promoter sequence responsible for bFGF-responsive transcription of the mrp3 gene.
- To characterize the FGF-regulatory element (FRE) within the mrp3 promoter.
Main Methods:
- Truncated mrp3 promoter sequences were analyzed to determine the minimal bFGF-responsive region.
- The identified FRE was tested for its ability to confer bFGF responsiveness when placed upstream of a thymidine kinase basal promoter.
Main Results:
- A minimal bFGF-responsive fragment containing a putative FGF-regulatory element (FRE) was identified within the mrp3 promoter.
- Nuclear factors in 3T3 cells bind to the FRE.
- The FRE demonstrated high transcriptional activity and bFGF responsiveness when linked to a heterologous promoter.
Conclusions:
- The FRE is a potent transcriptional element regulated by bFGF.
- The FRE likely plays a role in the transcriptional regulation of the mrp3 gene.
- The FRE may also regulate other FGF-responsive genes.