Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state

BMC Biol. 2010 Sep 27:8:128. doi: 10.1186/1741-7007-8-128.

Abstract

Background: A growing body of evidence has shown that Krüppel-like transcription factors play a crucial role in maintaining embryonic stem cell (ESC) pluripotency and in governing ESC fate decisions. Krüppel-like factor 5 (Klf5) appears to play a critical role in these processes, but detailed knowledge of the molecular mechanisms of this function is still not completely addressed.

Results: By combining genome-wide chromatin immunoprecipitation and microarray analysis, we have identified 161 putative primary targets of Klf5 in ESCs. We address three main points: (1) the relevance of the pathways governed by Klf5, demonstrating that suppression or constitutive expression of single Klf5 targets robustly affect the ESC undifferentiated phenotype; (2) the specificity of Klf5 compared to factors belonging to the same family, demonstrating that many Klf5 targets are not regulated by Klf2 and Klf4; and (3) the specificity of Klf5 function in ESCs, demonstrated by the significant differences between Klf5 targets in ESCs compared to adult cells, such as keratinocytes.

Conclusions: Taken together, these results, through the definition of a detailed list of Klf5 transcriptional targets in mouse ESCs, support the important and specific functional role of Klf5 in the maintenance of the undifferentiated ESC phenotype. See: http://www.biomedcental.com/1741-7007/8/125.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / genetics*
  • Chromatin Immunoprecipitation
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / physiology
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Expression Regulation, Developmental / physiology
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice
  • Microarray Analysis
  • Phenotype*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • Klf4 protein, mouse
  • Klf5 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • RNA-Binding Proteins
  • SERBP1 protein, mouse