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Related Experiment Video

Updated: May 1, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Dynamic estrogen receptor interactomes control estrogen-responsive trefoil Factor (TFF) locus cell-specific

Justine Quintin1, Christine Le Péron1, Gaëlle Palierne1

  • 1Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.

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Estrogen receptor (ER) binding sites dynamically regulate estrogen-sensitive genes by altering genome organization. This study reveals how ERBSs cooperate and show redundancy in controlling gene expression in breast cancer cells.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Epigenetics

Background:

  • Estradiol signaling involves the estrogen receptor (ER) regulating gene expression through DNA sequence, chromatin modifications, and genome organization.
  • Identifying specific ER binding sites (ERBSs) that regulate target genes, especially in clusters, remains a challenge.

Purpose of the Study:

  • Investigate the coordination of regulatory events at a large genomic locus containing estrogen-sensitive genes.
  • Determine how ER binding sites functionally link to specific gene regulation.
  • Explore the role of genome organization in ER-mediated transcriptional control.

Main Methods:

  • Analysis of a 2-Mb genomic locus with the estrogen-sensitive trefoil factor (TFF) gene cluster in breast cancer cells.
  • Utilized triplex-forming oligonucleotides to map functional links between ERBSs and gene regulation.
  • Assessed hormone- and cohesin-dependent changes in the 3D genome organization.

Main Results:

  • Demonstrated hormone- and cohesin-dependent reduction in the plasticity of the 3D genome organization at the TFF locus.
  • Showed that multiple ERBSs are dynamically brought near estrogen-sensitive genes.
  • Provided precise functional links between ER engagement at specific ERBSs and the regulation of particular genes.

Conclusions:

  • The 3D genome organization plays a crucial role in coordinating ER-mediated gene regulation.
  • Evidence supports the cooperation of enhancers in gene regulation.
  • Redundancy among ERBSs can occur, allowing for flexible gene control.