Transcriptional activation of the steroidogenic acute regulatory protein (StAR) gene: GATA-4 and CCAAT/enhancer-binding protein beta confer synergistic responsiveness in hormone-treated rat granulosa and HEK293 cell models

Mol Cell Endocrinol. 2006 Jun 27;252(1-2):92-101. doi: 10.1016/j.mce.2006.03.008. Epub 2006 May 8.


Steroidogenic acute regulatory protein (StAR) mediates translocation of cholesterol to the inner membranes of steroidogenic mitochondria, where it serves as a substrate for steroid synthesis. Transcription of StAR in the gonads and adrenal cells is upregulated by trophic hormones, involves downstream signaling pathways and a cohort of trans-factors acting as activators or suppressors of StAR transcription. This study suggests that a 21 basepair long sequence positioned at -81/-61 of the murine StAR promoter is sufficient to confer a robust hormonal activation of transcription in ovarian granulosa cells treated with FSH. We show that recombinant GATA-4 and CCAAT/enhancer-binding protein beta (C/EBPbeta) bind to the promoter at -66/-61 and -81/-70 and activate transcription of a reporter gene when co-expressed in heterologous human embryonic kidney 293 (HEK293) cells. In this cell model, C/EBPbeta and GATA-4 synergize in a sequence dependent manner and p300/CBP further maximizes their joint activities. Inhibitors of the transcriptional activators, such as liver-enriched inhibiting protein (C/EBPbeta-LIP), Friend of GATA-4 (FOG-2) protein and the viral E1A protein abolished the respective factor-dependent activities in HEK293 cells. Binding assays suggest that a dual binding of C/EBPbeta and GATA-4 to the promoter depends on the molar ratio of the factors present while demonstrating GATA-4 predominant association with the promoter DNA. This pattern may reflect on StAR expression at the time of corpus luteum formation when C/EBPbeta levels peak, as does StAR expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / physiology*
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Corpus Luteum / physiology
  • Female
  • GATA4 Transcription Factor / physiology*
  • Genes, Reporter
  • Granulosa Cells / physiology
  • Humans
  • Kidney
  • Phosphoproteins / genetics*
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic*
  • Transcriptional Activation
  • Transfection


  • CCAAT-Enhancer-Binding Protein-beta
  • GATA4 Transcription Factor
  • Phosphoproteins
  • steroidogenic acute regulatory protein
  • Chloramphenicol O-Acetyltransferase