Identifying estrogen receptor target genes

Willem-Jan Welboren1, Henk G Stunnenberg, Fred C G J Sweep

  • 1Department of Molecular Biology, NCMLS Radboud University Nijmegen, Nijmegen, The Netherlands.

Molecular Oncology
|April 23, 2009
PubMed

Insights

Identifying estrogen receptor (ER) genomic targets is crucial for breast cancer treatment. Chromatin immunoprecipitation coupled with genome-wide tiling arrays provides an unbiased method for identifying direct ER target sequences genome-wide.

Area of Science:

  • Molecular Biology
  • Genomics
  • Endocrinology

Background:

  • The estrogen receptor (ER) is a key transcription factor regulating genes vital in breast cancer.
  • ER activity influences patient response to endocrine therapies like tamoxifen.
  • Accurate identification of ER genomic targets is essential but challenging.

Purpose of the Study:

  • To present a robust method for identifying direct estrogen receptor (ER) genomic targets.
  • To overcome limitations of expression-based and in silico approaches for ER target discovery.

Main Methods:

  • Utilized Chromatin Immunoprecipitation (ChIP) to isolate ER-bound DNA fragments.
  • Employed genome-wide tiling arrays to map ER binding sites across the entire genome.
  • Combined ChIP with tiling arrays for unbiased, genome-wide identification of direct ER target sequences.

Main Results:

  • Successfully identified direct genomic target sites of the estrogen receptor (ER).
  • This ChIP-tiling array approach offers a comprehensive and unbiased view of ER binding.

Conclusions:

  • Chromatin immunoprecipitation coupled with genome-wide tiling arrays is an effective strategy for unbiased, genome-wide identification of direct ER target sequences.
  • This method advances our understanding of ER function in gene regulation and breast cancer.

Related Concept Videos

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:
Intracellular Hormone Receptors01:08

Intracellular Hormone Receptors

Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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.
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...
Reporter Genes02:11

Reporter Genes

Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.
Commonly used reporter...