A negative retinoic acid response element in the rat oxytocin promoter restricts transcriptional stimulation by heterologous transactivation domains. Academic Article uri icon

Overview

MeSH

  • Animals
  • Base Sequence
  • Carrier Proteins
  • Cells, Cultured
  • Cercopithecus aethiops
  • DNA-Binding Proteins
  • Molecular Sequence Data
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Rats
  • Receptors, Retinoic Acid
  • Transcription, Genetic

MeSH Major

  • Gene Expression Regulation
  • Oxytocin
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Transcriptional Activation
  • Tretinoin

abstract

  • Retinoic acid receptors are ligand-dependent transcription factors that stimulate gene transcription from promoters containing retinoic acid or thyroid hormone response elements. We describe a high-affinity binding site from the rat oxytocin promoter that mediates negative transcriptional regulation by the retinoic acid receptor. To examine whether strong, constitutive transactivation domains would be capable of stimulating gene transcription when bound to this DNA binding site that normally mediates transcriptional repression, we fused the transactivation domain of the herpes simplex viral protein VP16 to the amino terminus of the retinoic acid receptor and tested the activity of the chimeric protein on the negative retinoic acid response element. This chimeric retinoic acid receptor acted as a strong, constitutive transactivator when bound to promoters containing palindromic thyroid hormone/retinoic acid response elements but surprisingly it still repressed gene transcription when bound to promoters containing the oxytocin-negative retinoic acid response element. These results suggest that a negative DNA binding site itself can inhibit the function of even potent constitutive transactivation domains, and provide evidence that tethering of a constitutive transactivation domain to DNA is insufficient to activate gene transcription.

publication date

  • February 15, 1992

has subject area

  • Animals
  • Base Sequence
  • Carrier Proteins
  • Cells, Cultured
  • Cercopithecus aethiops
  • DNA-Binding Proteins
  • Gene Expression Regulation
  • Molecular Sequence Data
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Oxytocin
  • Promoter Regions, Genetic
  • Rats
  • Receptors, Retinoic Acid
  • Regulatory Sequences, Nucleic Acid
  • Transcription, Genetic
  • Transcriptional Activation
  • Tretinoin

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC48418

PubMed ID

  • 1311087

Additional Document Info

start page

  • 1209

end page

  • 1213

volume

  • 89

number

  • 4