title: Krüppel-like factor 4 regulates genetic stability in mouse embryonic fibroblasts.
abstract: BACKGROUND
  Krüppel-like factor 4 (KLF4) is a member of the KLF family of transcription factors and regulates proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers including colorectal cancer. We previously showed that KLF4 inhibits cell cycle progression following DNA damage and that mouse embryonic fibroblasts (MEFs) null for Klf4 are genetically unstable, as evidenced by increased rates of cell proliferation, and the presence of DNA double strand breaks (DSBs), centrosome amplification, chromosome aberrations and aneuploidy.
  
  
  METHODS
  To determine whether re-expression of Klf4 corrects the observed genetic instability in MEFs null for Klf4 (Klf4(-/-)), we transfected Klf4(-/-)MEFs with Klf4-expressing plasmids and compared the results to wild type (Klf4(+/+)) and untransfected or mock-transfected Klf4(-/-)MEFs.
  
  
  RESULTS
  We show that overexpression of Klf4 in Klf4(-/-)MEFs reduced cell proliferation rates and the proportion of cells with DSBs, abnormal centrosome numbers, aneuploidy and micronuclei. In addition, Klf4-transfected Klf4(-/-)MEFs exhibited a more robust DNA damage repair response as demonstrated by the greater rate in disappearance of γ-H2AX and 53BP1 foci following γ-irradiation.
  
  
  CONCLUSIONS
  Taken together these findings provide evidence that KLF4 plays a crucial role in the maintenance of genetic stability by modulating the DNA damage response and repair processes.
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Enas A
authors.initials: EA
authors.lastname: El-Karim
authors.forename: Engda G
authors.initials: EG
authors.lastname: Hagos
authors.forename: Amr M
authors.initials: AM
authors.lastname: Ghaleb
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Yang
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D055786:Gene Knockout Techniques; D042822:Genomic Instability; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D014162:Transfection
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors
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