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The Estrogen Receptor α-Cistrome Beyond Breast Cancer.

Published on Aug 4, 2016in Molecular Endocrinology3.628
· DOI :10.1210/ME.2016-1062
Marjolein Droog8
Estimated H-index: 8
(NKI-AVL: Netherlands Cancer Institute),
Mark Mensink3
Estimated H-index: 3
(NKI-AVL: Netherlands Cancer Institute),
Wilbert Zwart27
Estimated H-index: 27
(NKI-AVL: Netherlands Cancer Institute)
Abstract
Although many tissues express estrogen receptor (ER)α, most studies focus on breast cancer where ERα occupies just a small fraction of its total repertoire of potential DNA-binding sites, based on sequence. This raises the question: Can ERα occupy these other potential binding sites in a different context? Ligands, splice variants, posttranslational modifications, and acquired mutations of ERα affect its conformation, which may alter chromatin interactions. To date, literature describes the DNA-binding sites of ERα (the ERα cistrome) in breast, endometrium, liver, and bone, in which the receptor mainly binds to enhancers. Chromosomal boundaries provide distinct areas for dynamic gene regulation between tissues, where the usage of enhancers deviates. Interactions of ERα with enhancers and its transcriptional complex depend on the proteome, which differs per cell type. This review discusses the biological variables that influence ERα cistromics, using reports from human specimens, cell lines, and mouse tiss...
  • References (175)
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#2Ekaterina Nevedomskaya (NKI-AVL: Netherlands Cancer Institute)H-Index: 17
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Tamoxifen, a small molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERα was foun...
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#1Koen D. Flach (NKI-AVL: Netherlands Cancer Institute)H-Index: 7
#2Wilbert Zwart (NKI-AVL: Netherlands Cancer Institute)H-Index: 27
The advent of genome-wide transcription factor profiling has revolutionized the field of breast cancer research. Estrogen receptor α (ERα), the major drug target in hormone receptor-positive breast cancer, has been known as a key transcriptional regulator in tumor progression for over 30 years. Even though this function of ERα is heavily exploited and widely accepted as an Achilles heel for hormonal breast cancer, only since the last decade we have been able to understand how this transcription ...
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