title: Regulation of the FGF-4 gene by a complex distal enhancer that functions in part as an enhanceosome.
abstract: 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.
authors.affiliation: 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.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Luster
authors.forename: Angie
authors.initials: A
authors.lastname: Rizzino
mesh_terms: 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
chemical_list: 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