NANOG promoter methylation and expression correlation during normal and malignant human germ cell development

Daniel Nettersheim, Katharina Biermann, Ad J M Gillis, Klaus Steger, Leendert H J Looijenga, Hubert Schorle

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


Testicular germ cell tumors are the most frequent malignant tumors in young Caucasian males, with increasing incidence. The actual model of tumorigenesis is based on the theory that a block in maturation of fetal germ cells lead to formation of the intratubular germ cell neoplasia unclassified. Early fetal germ cells and undifferentiated germ cell tumors express pluripotency markers such as the transcription factor NANOG. It has been demonstrated, that epigenetic modifications such as promoter DNA-methylation is able to silence gene expression in normal and cancer cells. Here we show, that OCT3/4-SOX2 mediated expression of NANOG can be silenced by methylation of promoter CpG-sites. We found that global methylation of DNA decreased from fetal spermatogonia to mature sperm. In contrast, CpGs in the NANOG promoter were found hypomethylated in spermatogonia and hypermethylated in sperm. This selective repression might reflect the cells need to suppress pluripotency in order to prevent malignant transformation. Finally, methylation of CpGs in the NANOG promoter in germ cell tumors and derived cell lines correlated to differentiation state.

Original languageEnglish
Pages (from-to)114-22
Number of pages9
Issue number1
Publication statusPublished - Jan 2011
Externally publishedYes


  • Cell Differentiation/physiology
  • Cell Line, Tumor
  • CpG Islands/physiology
  • DNA Methylation
  • Gene Silencing
  • Homeodomain Proteins/genetics
  • Humans
  • Male
  • Nanog Homeobox Protein
  • Neoplasms, Germ Cell and Embryonal/genetics
  • Promoter Regions, Genetic
  • Spermatogonia/metabolism
  • Spermatozoa/metabolism


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