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Updated: Apr 26, 2026

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

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Transient estrogen receptor binding and p300 redistribution support a squelching mechanism for estradiol-repressed

Michael J Guertin1, Xuesen Zhang, Scott A Coonrod

  • 1Laboratory of Receptor Biology and Gene Expression (M.J.G., G.L.H.), National Cancer Institute, Bethesda, Maryland 20892; State Key Laboratory of Reproductive Medicine (X.Z.), Nanjing Medical University, Nanjing 210029, China; and Baker Institute for Animal Health (X.Z., S.A.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.

Molecular Endocrinology (Baltimore, Md.)
|July 23, 2014
PubMed

Insights

Estrogen receptor alpha (ER) master regulators repress genes by transiently binding and hijacking coactivators, redirecting them to activate other genes, revealing a new gene regulation mechanism.

Area of Science:

  • Molecular Biology
  • Genomics
  • Epigenetics

Background:

  • Gene regulation is crucial for development and response to stimuli.
  • Master regulators orchestrate gene activation and repression.
  • Estrogen receptor alpha (ER) is a known transcriptional activator, but its role in gene repression is unclear.

Purpose of the Study:

  • To investigate the mechanisms of immediate gene repression mediated by ER upon estrogen stimulation.
  • To analyze context-specific gene regulation in response to estradiol (E2).

Main Methods:

  • Integrated genomic transcription, chromosome looping, transcription factor binding, and chromatin structure data.
  • Analyzed E2-induced signaling in human MCF-7 breast cancer cells.
  • Compared molecular characteristics of repressed, activated, and unregulated genes.

Main Results:

  • Identified a class of genes immediately repressed upon estrogen stimulation.
  • Observed transient binding of ER to repressed genes at early time points.
  • Found that p300 coactivator redistributes from non-ER to ER enhancers after E2 treatment.

Conclusions:

  • ER-mediated gene repression involves transient binding and coactivator sequestration.
  • Supports an extended "physiological squelching" model for gene regulation.
  • ER hijacks coactivators from repressed genes to activate other target genes.

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