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Related Concept Videos

Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
The Two-State Receptor Model01:29

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...

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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
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Cooperative estrogen receptor interaction with consensus or variant estrogen responsive elements in vitro.

C M Klinge1, F V Peale, R Hilf

  • 1Department of Biochemistry, University of Rochester School of Medicine and Dentistry, New York 14642.

Cancer Research
|March 11, 1992
PubMed
Summary

Estrogen receptor (ER) binds to estrogen-responsive elements (EREs) with high affinity. Cooperative binding occurs with multiple EREs, influenced by sequence and spacing, controlling gene expression.

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Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Estrogen receptor (ER) plays a crucial role in regulating gene expression.
  • Estrogen-responsive elements (EREs) are DNA sequences that mediate ER binding.
  • Understanding ER-ERE interactions is key to deciphering hormonal regulation of genes.

Purpose of the Study:

  • To investigate the binding kinetics and affinity of calf uterine ER to EREs in vitro.
  • To determine the structural requirements of EREs for high-affinity ER binding.
  • To explore the cooperative binding of ER to multiple EREs and its implications.

Main Methods:

  • In vitro binding assays using purified calf uterine ER and synthetic ERE sequences cloned into a plasmid vector.
  • Characterization of ER-ERE interactions using Scatchard and Hill analyses.
  • Synthesis and testing of variant ERE sequences to assess binding affinity and cooperativity.

Main Results:

  • Dimeric ER binds to single EREs with high affinity (Kd ≈ 0.24 nM).
  • Cooperative ER binding was observed with three or more tandem EREs (Hill coefficients > 1.5).
  • ERE sequence and spacing of inverted repeats critically influence ER binding affinity and cooperativity.

Conclusions:

  • In vitro findings confirm cooperative ER binding to EREs, mirroring in vivo observations.
  • ERE sequence, spacing, and copy number precisely regulate ER binding to target genes.
  • This study provides insights into the molecular mechanisms of estrogen-regulated gene expression.