The exact mechanisms by which enhancers regulate transcription are currently under investigation. For some genes, activation is accomplished by an intricate array of enhancer cis-regulatory elements that direct the assembly of a gene-specific activation complex known as an "enhanceosome". Transcription of the fibroblast growth factor-4 (FGF-4) gene during early development is controlled by a powerful distal enhancer located 3 kb downstream of the transcription start site within the 3' untranslated region of the gene. Previous studies have shown that FGF-4 enhancer function is mediated by at least three critical positive cis-regulatory elements: an HMG, a POU, and a GT-box motif, which bind the transcription factors Sox-2, Oct-3, and Sp1/Sp3, respectively. In this study, we identify a second essential HMG motif within the FGF-4 enhancer that binds the transcription factor Sox-2. Moreover, we demonstrate that spatial alignment of the new HMG motif, relative the other enhancer cis-regulatory elements, is important. Based on findings presented in this report, and work published earlier, we propose that the previously identified core HMG and POU cis-regulatory elements of the FGF-4 enhancer are dependent on one another and function in an enhanceosome-like manner. In contrast, the HMG motif identified in this study is only partially dependent on the other enhancer cis-regulatory elements for its function.
- EC cells
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