Cited by 83Estrogen and related hormone effectsGenomics and Chromatin DynamicsEpigenetics and DNA Methylation

Long-Range Activation of GREB1 by Estrogen Receptor via Three Distal Consensus Estrogen-Responsive Elements in Breast Cancer Cells

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Sun, Jun, Nawaz, Zafar, Slingerland, Joyce M.·2007·Molecular Endocrinology

Abstract

The estrogen receptor (ER) binds to estrogen-responsive elements (EREs) to activate gene transcription. The best characterized EREs are located in proximal gene promoters, but recent data indicate that only a minority of ER binding sites lie within proximal promoter regions. GREB1 (gene regulated by estrogen in breast cancer 1) is an ER target gene that regulates estrogen-induced proliferation in breast cancer cells. We identified three consensus EREs, located at −21.2, −9.5, and −1.6 kb upstream of the closest GREB1a transcription start site that appear to mediate long-range GREB1 gene activation by ER. All three ERE sites nucleate ER, steroid receptor coactivator-3 (SRC-3), and RNA polymerase II (Pol II) and undergo histone acetylation in response to estradiol. Estrogen-stimulated ER binding at all three EREs was cyclic and synchronous. SRC-3 and Pol II recruitment to all three EREs was activated by estrogen but not tamoxifen. In contrast, estrogen stimulated only Pol II and not ER or SRC-3 recruitment to the GREB1 core promoter regions. Long-range histone acetylation, centered on the three ERE motifs and the GREB1 core promoters, was observed in response to estrogen but not to tamoxifen. These data suggest that estrogen-stimulated GREB1 transcription may involve coordinated ER binding to all three distal consensus ERE motifs. Long-range activation by ER acting at multiple EREs may be more common than previously appreciated.

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  1. Deschenes J, Bourdeau V, White JH, Mader S 2006 Long-range regulation of the GREB1 gene by estrogen receptor ␣ in breast cancer cell line MCF-7. Nuclear receptors: bench to bedside. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 104

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Authors
Sun, J., Nawaz, Z., & Slingerland, J. M.
Affiliations
  • Braman Family Breast Cancer Institute (J.S., Z.N., J.M.S.),Miami, Florida 33136
  • University of Miami (US)
Corresponding author
  • Sun, Jun
  • Slingerland, Joyce M.
Venue
Molecular Endocrinology
Published
2007-11-01
Volume
21
Issue
11
Pages
2651-2662
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
OpenAlex
W2153843576
Cited by
83
References
40
Citations by year
2026: 1 · 2025: 3 · 2023: 4 · 2021: 5 · 2020: 9 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 8 · 2013: 2 · 2012: 8
FWCI
3.04
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Miami
  • Sylvester Comprehensive Cancer Center, University of Miami Health Systems
  • Leonard M. Miller School of Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
GREB1, estrogen receptor, estrogen response element, breast cancer cells, SRC-3, RNA polymerase II recruitment, histone acetylation, estradiol, tamoxifen, transcriptional regulation, core promoter
MeSH terms
Base Sequence, Breast Neoplasms, Enzyme Activation, Estradiol, Estrogens, Humans, Molecular Sequence Data, Neoplasm Proteins, Promoter Regions, Genetic, Receptors, Estrogen, Tamoxifen, Transcription, Genetic, Trans-Activators, Amino Acid Motifs, Cell Line, Tumor, Histone Acetyltransferases, Nuclear Receptor Coactivator 3

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