Krüppel-like factor 6 expression changes during trophoblast syncytialization and transactivates ßhCG and PSG placental genes

PLoS One. 2011;6(7):e22438. doi: 10.1371/journal.pone.0022438. Epub 2011 Jul 22.


Background: Krüppel-like factor-6 (KLF6) is a widely expressed member of the Sp1/KLF family of transcriptional regulators involved in differentiation, cell cycle control and proliferation in several cell systems. Even though the highest expression level of KLF6 has been detected in human and mice placenta, its function in trophoblast physiology is still unknown.

Methodology/principal findings: Herein, we explored KLF6 expression and sub-cellular distribution in human trophoblast cells differentiating into the syncytial pathway, and its role in the regulation of genes associated with placental development and pregnancy maintenance. Confocal immunofluorescence microscopy demonstrated that KLF6 is expressed throughout human cytotrophoblast differentiation showing no evident modifications in its nuclear and cytoplasmic localization pattern. KLF6 transcript and protein peaked early during the syncytialization process as determined by qRT-PCR and western blot assays. Overexpression of KLF6 in trophoblast-derived JEG-3 cells showed a preferential nuclear signal correlating with enhanced expression of human β-chorionic gonadotropin (βhCG) and pregnancy-specific glycoprotein (PSG) genes. Moreover, KLF6 transactivated βhCG5, PSG5 and PSG3 gene promoters. Deletion of KLF6 Zn-finger DNA binding domain or mutation of the consensus KLF6 binding site abolished transactivation of the PSG5 promoter.

Conclusions/significance: Results are consistent with KLF6 playing a role as transcriptional regulator of relevant genes for placental differentiation and physiology such as βhCG and PSG, in agreement with an early and transient increase of KLF6 expression during trophoblast syncytialization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation*
  • Cell Line
  • Chorionic Gonadotropin, beta Subunit, Human / genetics*
  • Female
  • Humans
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice
  • Placenta / cytology
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Proteins / genetics*
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors
  • Transcription, Genetic
  • Transcriptional Activation*
  • Trophoblasts / cytology*
  • Trophoblasts / metabolism


  • Biomarkers
  • Chorionic Gonadotropin, beta Subunit, Human
  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • Pregnancy Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger