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Updated: Jun 23, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
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.
Abstract:
The estrogen receptor (ER) is a ligand inducible transcription factor that regulates a large number of target genes. These targets are particularly relevant in breast cancer, where the sensitivity of the tumor to estrogens determines whether the patients can be treated with endocrine therapy such as tamoxifen. Identifying genomic ER targets is a daunting task. Quantifying expression levels of suspected target genes after estradiol stimulation or, more recently, using expression microarrays to this effect will reveal which genes are regulated by estradiol, however, without discriminating between direct and indirect targets. The identification of the palindromic sequence that defines the estrogen responsive element (ERE) allows for the in silico discovery of putative ER targets in the genome. However the ER can also bind imperfect EREs and half sites, and can bind indirectly via other factors. Chromatin immunoprecipitation (ChIP) can yield all ER genomic target sites. Coupling of ChIP with genome-wide tiling arrays allows for the genome-wide unbiased identification of direct ER target sequences.
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.
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