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Updated: Jul 18, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Ligand-specific dynamics of the androgen receptor at its response element in living cells

Tove I Klokk1, Piotr Kurys, Cem Elbi

  • 1Department of Molecular Biosciences, University of Oslo, Postboks 1041 Blindern, 0316 Oslo, Norway.

Molecular and Cellular Biology
|December 26, 2006
PubMed

Insights

Androgen receptor (AR) interactions with DNA differ between activators and inhibitors. This study reveals distinct kinetic mechanisms for AR regulation, impacting gene expression in health and disease.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Endocrinology

Background:

  • Androgens are crucial for male physiology and prostate cancer, acting via the androgen receptor (AR).
  • Antiandrogens are used clinically, but their in vivo mechanisms remain unclear.
  • AR is a ligand-modulated transcription factor regulating gene expression.

Purpose of the Study:

  • To elucidate the in vivo kinetic and mechanistic differences in androgen receptor (AR) interactions with target genomic sites.
  • To investigate the role of chromatin remodeling and AR intramolecular interactions in AR function.

Main Methods:

  • Live-cell imaging using fluorescent resonance energy transfer (FRET) to analyze AR dynamics.
  • Studying wild-type AR and transcriptionally compromised mutants.
  • Observing recruitment of the BRM ATPase complex and chromatin remodeling.

Main Results:

  • Agonist-bound AR exhibits slower interaction with genomic sites, coupled with chromatin remodeling and transcriptional activation.
  • Antagonist-bound or mutant AR shows faster interaction without chromatin remodeling, leading to lack of transcriptional inhibition.
  • Intramolecular N- and C-terminal interactions of AR are critical for function in vivo.

Conclusions:

  • Distinct kinetic profiles govern AR transcriptional regulation by androgens and antiandrogens.
  • Chromatin remodeling and AR intramolecular interactions are key mechanistic determinants of AR activity.
  • These findings provide a basis for understanding AR regulation in physiological and pathological contexts, including prostate cancer.

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