Bimodal, reciprocal regulation of fibroblast growth factor receptor 1 promoter activity by BTEB1/KLF9 during myogenesis.
Expression of the gene encoding fibroblast growth factor receptor 1 (FGFR1) and subsequent FGFR1-mediated cell signaling controls numerous developmental and disease-related processes. The transcriptional regulation of the FGFR1 gene is central to these developmental events and serves as a molecular model for understanding transcriptional control of growth factor receptor genes. The FGFR1 promoter is activated in proliferating myoblasts via several Sp1-like binding elements. These elements display varying levels of activation potential, suggesting that unique protein-DNA complexes coordinate FGFR1 gene expression via each of these sites. The Krüppel-like factor, BTEB1/KLF9, was expressed in both proliferating myoblasts and differentiated myotubes in vitro. The BTEB1 protein was nuclear-localized in both cell types. BTEB1 activated the FGFR1 promoter via interaction with the Sp1-like binding site located at -59 bp within the FGFR1 promoter. FGFR1 gene expression is down-regulated during myogenic differentiation, and FGFR1 promoter activity is correspondingly reduced. This reduction in FGFR1 promoter activity was attributable to BTEB1 interaction with the same Sp1-like binding site located at -59 bp in the FGFR1 promoter. Therefore, BTEB1 is capable of functioning as a transcriptional activator and repressor of the same promoter via the same DNA-binding element and demonstrates a novel, bimodal role of BTEB1 during myogenesis.
Mitchell
Darrion L
DL
Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
DiMario
Joseph X
JX
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002645:Chickens; D047369:Chromatin Immunoprecipitation; D004252:DNA Mutational Analysis; D004330:Drosophila; D018507:Gene Expression Regulation, Developmental; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D016296:Mutagenesis; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism
D051741:Kruppel-Like Transcription Factors; D016329:Sp1 Transcription Factor; D051496:Receptor, Fibroblast Growth Factor, Type 1