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Updated: Jun 4, 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

Multiple sequence-specific DNA-binding proteins mediate estrogen receptor signaling through a tethering pathway

Nina Heldring1, Gary D Isaacs, Adam G Diehl

  • 1Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.

Molecular Endocrinology (Baltimore, Md.)
|February 19, 2011
PubMed

Insights

Estrogen receptors (ERs) use a tethering pathway to bind DNA via other transcription factors. This study reveals new insights into ligand-dependent activation and identifies key genes regulated by this mechanism.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Estrogen signaling pathways are crucial in cellular processes.
  • The indirect recruitment (tethering) of estrogen receptors (ERs) to DNA is a key mechanism.
  • Limited understanding exists regarding ligand-dependent activation in ER tethering pathways.

Purpose of the Study:

  • To investigate the mechanisms of ligand-dependent activation in estrogen receptor tethering.
  • To identify transcription factors involved in ER tethering to DNA.
  • To define genes regulated by ERα tethering through specific transcription factors.

Main Methods:

  • Proteomic analyses to identify protein interactions.
  • Genomic analyses to map DNA binding sites.
  • Gene-specific assays to confirm regulatory roles.

Main Results:

  • A broad range of DNA-binding transcription factors contribute to estrogen signaling via tethering.
  • ERα tethering through activator protein 1 (e.g., c-Fos) and cAMP response element-binding protein (CREB) family members mediates estrogen responsiveness for specific genes.
  • Functional interplay between c-Fos and CREB1 is critical for estrogen-dependent regulation in the tethering pathway.

Conclusions:

  • ERα recruitment in the tethering pathway is ligand-dependent.
  • Formation of transcription factor complexes involving interplay between different protein families drives ERα recruitment.
  • This study elucidates a novel mechanism of estrogen signaling regulation through transcription factor interplay.

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