Basic fibroblast growth factor transcriptional autoregulation requires EGR-1.
Basic fibroblast growth factor (bFGF) is an important growth factor for neuroectoderm- and mesoderm-derived cells. In addition bFGF is an important angiogenic factor and appears to contribute to tumorigenesis. This is exemplified by the fact that bFGF is expressed in a large majority of human gliomas and that bFGF expression is critical for the growth and tumorigenesis of these cells. It has been shown previously that bFGF can induce its own expression through an increase in bFGF mRNA. In this report, we show that bFGF leads to its own synthesis through an autoregulated transcriptional response that requires the transcription factor Egr-1 (also known as Krox24, Zif268 and NGFI-A). Egr-1 binds to two DNA elements in the bFGF promoter and positively regulates transcription. Mutation of these sites blocks the ability of bFGF to transcriptionally regulate the bFGF promoter. These data indicate a mechanism to explain how bFGF functions to autoregulate its expression and demonstrate that Egr-1 is as an essential transcription factor in this process.
Wang
D
D
Lineberger Comprehensive Cancer Center and Department of Biology, University of North Carolina, Chapel Hill 27599-7295, USA.
Mayo
M W
MW
Baldwin
A S
AS
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2