AP-2 alpha suppresses skeletal myoblast proliferation and represses fibroblast growth factor receptor 1 promoter activity.
Skeletal muscle development is partly characterized by myoblast proliferation and subsequent differentiation into postmitotic muscle fibers. Developmental regulation of expression of the fibroblast growth factor receptor 1 (FGFR1) gene is required for normal myoblast proliferation and muscle formation. As a result, FGFR1 promoter activity is controlled by multiple transcriptional regulatory proteins during both proliferation and differentiation of myogenic cells. The transcription factor AP-2 alpha is present in nuclei of skeletal muscle cells and suppresses myoblast proliferation in vitro. Since FGFR1 gene expression is tightly linked to myoblast proliferation versus differentiation, the FGFR1 promoter was examined for candidate AP-2 alpha binding sites. Mutagenesis studies indicated that a candidate binding site located at -1035 bp functioned as a repressor cis-regulatory element. Furthermore, mutation of this site alleviated AP-2 alpha-mediated repression of FGFR1 promoter activity. Chromatin immunoprecipitation studies demonstrated that AP-2 alpha interacted with the FGFR1 promoter in both proliferating myoblasts and differentiated myotubes. In total, these results indicate that AP-2 alpha is a transcriptional repressor of FGFR1 gene expression during skeletal myogenesis.
Mitchell
Darrion L
DL
Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
DiMario
Joseph X
JX
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002645:Chickens; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000502:physiology*; D014162:Transfection
D050656:Transcription Factor AP-2; D004247:DNA; D051496:Receptor, Fibroblast Growth Factor, Type 1