The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner.
The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both in keratinocytes and in fibroblasts during development and tissue regeneration. Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF but not by FGF-2. In fibroblasts it was stimulated by FGF-2 but not by EGF. Likewise, the recently discovered FGF-inducible response element (FiRE) on the gene of syndecan-1 was stimulated by FGF-2 in fibroblasts and by EGF in keratinocytes, but not vice versa. The FiRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1). The growth factor-stimulated binding of these transcription factors, as well as their requirement for FiRE activation, varied between the two cell types. First, although AP-1s were required for activation of FiRE in both cell types, the binding of AP-1 to FiRE was increased by growth factor-stimulation only in fibroblasts and not in keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE in fibroblasts. Thirdly, EGF, which did not activate FiRE in fibroblasts, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FiRE in keratinocytes was not needed in fibroblasts. These data suggest mechanisms by which members of the EGF- and FGF-families can differentially stimulate transcription through AP-1 regulated elements in a cell type-specific manner.
Turku Centre for Biotechnology, University of Turku, Finland.
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P
Jaakkola
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Määttä
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Jalkanen
D016475:3T3 Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects*; D053668:Syndecan-1; D053667:Syndecans; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; C464944:Emr4 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011506:Proteins; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor