Identification and characterization of the minimal promoter of Mipu1: the role of GC boxes in the regulation of basal transcription

Acta Biochim Biophys Sin (Shanghai). 2009 Apr;41(4):309-15. doi: 10.1093/abbs/gmp019.

Abstract

Mipu1, a novel gene encoding a KRAB/C2H2 zinc finger protein, was first reported to be up-regulated in myocardial ischemia-reperfusion injury, functioning to protect cells against oxidative stress. To map the promoter region of the gene and to understand its regulation, we identified the transcription start site and revealed that the 1366-bp fragment upstream of the transcription start site possesses promoter activity. Deletion constructs of the 5'-flanking region of Mipu1 lead to the identification of a minimal promoter, in which neither a TATA box nor a CAAT box was detected. Two GC boxes were found; however, they are the specific binding sites for Sp1-family transcription factors. Mutations in these GC boxes resulted in the total loss of Mipu1 minimal promoter activity. Finally, WP631, an Sp1-family-specific inhibitor, was found to decrease the promoter activity in a dose-dependent manner, indicating that the GC boxes are essential for the activity of the Mipu1 minimal promoter activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Flanking Region / genetics
  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Binding Sites / physiology
  • Cell Line
  • Daunorubicin / analogs & derivatives
  • Daunorubicin / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation*
  • Luciferases, Renilla / genetics
  • Luciferases, Renilla / metabolism
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic / genetics*
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics*
  • Sp1 Transcription Factor / antagonists & inhibitors
  • Sp1 Transcription Factor / metabolism
  • Transcription Initiation Site
  • Transcription, Genetic / drug effects
  • Transfection

Substances

  • Mipu1 protein, rat
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Sp1 Transcription Factor
  • WP 631
  • Luciferases, Renilla
  • Daunorubicin