NANOG gene expression is regulated by the ETS transcription factor ETV4 in human embryonic carcinoma NCCIT cells

Biochem Biophys Res Commun. 2017 Jun 3;487(3):532-538. doi: 10.1016/j.bbrc.2017.04.059. Epub 2017 Apr 13.

Abstract

We demonstrated that ETV4 is a transcriptional activator of the NANOG gene in human embryonic carcinoma NCCIT cells. The endogenous expression of NANOG and ETV4 in naïve cells was significantly down-regulated upon differentiation and by shRNA-mediated knockdown of ETV4. NANOG transcription was significantly upregulated by ETV4 overexpression. A putative ETS binding site (EBS) is present in the region (-285 to -138) of the proximal promoter. Site-directed mutagenesis of the putative EBS (-196AGGATT-191) abolished NANOG promoter activity and ETV4 interacted with this putative EBS both in vivo and in vitro. Our data provide the molecular details of ETV4-mediated NANOG gene expression.

Keywords: ETV4; Embryonic carcinoma NCCIT; NANOG promoter.

MeSH terms

  • Adenovirus E1A Proteins / metabolism*
  • Embryonal Carcinoma Stem Cells / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Nanog Homeobox Protein / genetics*
  • Nanog Homeobox Protein / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-ets
  • Tumor Cells, Cultured

Substances

  • Adenovirus E1A Proteins
  • ETV4 protein, human
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets