title: Repression of myoblast proliferation and fibroblast growth factor receptor 1 promoter activity by KLF10 protein.
abstract: BACKGROUND
  FGFR1 gene expression regulates myoblast proliferation and differentiation, and its expression is controlled by Krüppel-like transcription factors.
  
  
  RESULTS
  KLF10 interacts with the FGFR1 promoter, repressing its activity and cell proliferation.
  
  
  CONCLUSIONS
  KLF10 represses FGFR1 promoter activity and thereby myoblast proliferation.
  
  
  CONCLUSIONS
  A model of transcriptional control of chicken FGFR1 gene regulation during myogenesis is presented. Skeletal muscle development is controlled by regulation of myoblast proliferation and differentiation into muscle fibers. Growth factors such as fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate cell proliferation and differentiation in numerous tissues, including skeletal muscle. Transcriptional regulation of FGFR1 gene expression is developmentally regulated by the Sp1 transcription factor, a member of the Krüppel-like factor (KLF) family of transcriptional regulators. Here, we show that another KLF transcription factor, KLF10, also regulates myoblast proliferation and FGFR1 promoter activity. Expression of KLF10 reduced myoblast proliferation by 86%. KLF10 expression also significantly reduced FGFR1 promoter activity in myoblasts and Sp1-mediated FGFR1 promoter activity in Drosophila SL2 cells. Southwestern blot, electromobility shift, and chromatin immunoprecipitation assays demonstrated that KLF10 bound to the proximal Sp factor binding site of the FGFR1 promoter and reduced Sp1 complex formation with the FGFR1 promoter at that site. These results indicate that KLF10 is an effective repressor of myoblast proliferation and represses FGFR1 promoter activity in these cells via an Sp1 binding site.
authors.affiliation: Department of Cell Biology and Anatomy, School of Graduate and Postdoctoral Studies and Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: Rajini
authors.initials: R
authors.lastname: Parakati
authors.forename: Joseph X
authors.initials: JX
authors.lastname: DiMario
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D016384:Consensus Sequence; D004330:Drosophila; D051765:Early Growth Response Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D016329:Sp1 Transcription Factor; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Cell Proliferation; DNA Transcription; Fibroblast Growth Factor Receptor (FGFR); Gene Regulation; Myogenesis