Related Experiment Video

Updated: May 31, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

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Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer

Stephen Safe1, Evan Farkas1, Amanuel E Hailemariam1

  • 1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.

Cancers
|January 25, 2025
PubMed

Insights

Nuclear receptors (NRs) and Sp transcription factors (TFs) form complexes to regulate gene expression indirectly. This NR/Sp complex interaction offers new therapeutic targets for various diseases.

Area of Science:

  • Molecular Biology
  • Genetics
  • Pharmacology

Background:

  • The human nuclear receptor (NR) superfamily comprises 48 ligand-activated transcription factors crucial for cellular homeostasis and disease.
  • NRs are key drug targets, with ligands modulating gene expression via agonists, antagonists, or inverse agonists.
  • Classical NR mechanisms involve DNA binding as monomers, dimers, or heterodimers to response elements.

Purpose of the Study:

  • To identify Sp-regulated genes indirectly coregulated by nuclear receptors (NRs).
  • To elucidate the mechanism of NR-Sp complex formation and function in gene regulation.
  • To highlight the therapeutic potential of targeting NR-Sp interactions.

Main Methods:

  • Review of existing studies on NR-regulated genes and transcription factor binding.
  • Analysis of promoter regions for NR and Sp transcription factor binding sites.
  • Investigation of NR-Sp complex formation and its impact on gene expression.

Main Results:

  • Many NR-regulated genes lack direct NR cis-element binding; their promoters bind Sp1, Sp3, and Sp4 transcription factors.
  • Nuclear receptors directly bind Sp1, Sp3, or Sp4, forming NR/Sp complexes that bind GC-rich sites.
  • NR-responsive genes contain cis-elements binding both Sp TFs and NRs, with mutations affecting inducibility and basal expression.

Conclusions:

  • Gene regulation by NRs often involves indirect coregulation through Sp transcription factors.
  • NR/Sp complexes act as crucial mediators of gene expression, influenced by NR ligands.
  • Targeting NRs or inducing Sp TF degradation presents a dual therapeutic strategy for NR-responsive genes.
Keywords:
NR/Sp complexesSp transcription factorsgene regulationnuclear receptor

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