Regulation of the FGF-4 gene by a complex distal enhancer that functions in part as an enhanceosome.
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.
Luster
Troy A
TA
Eppley Institute for the Research in Cancer and Allied Diseases, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Rizzino
Angie
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002457:Cell Extracts / Q000737:chemistry; D045744:Cell Line, Tumor; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D024742:HMG-Box Domains / Q000235:genetics; D024002:HMGB Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D051519:Fibroblast Growth Factor 4; D024002:HMGB Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D005346:Fibroblast Growth Factors; D015500:Chloramphenicol O-Acetyltransferase