Identification of the sequences within the human complement 3 promoter required for estrogen responsiveness provides insight into the mechanism of tamoxifen mixed agonist activity

Molecular Endocrinology
J D FanD P McDonnell

Abstract

The promoter of the human C3 gene has been shown to be responsive to stimulation by both estrogen and tamoxifen-activated estrogen receptor (ER) in transcriptional assays reconstituted in mammalian cells. Using a series of deletions and point mutations, we have determined that the agonist activity of these two compounds was dependent upon the direct interaction of ER with each of three estrogen response elements (EREs) contained within this promoter. One of these sequences, ERE1 resembles the canonical vitellogenin A2-ERE whereas the other two, ERE2 and ERE3, do not display significant homology to known EREs. Using gene transfer studies it was shown that these sequences are necessary and sufficient for ER-mediated transcription. Interestingly, using in vitro receptor/DNA-binding assays we demonstrated that neither ERE1, ERE2, or ERE3 alone formed high-affinity complexes with purified ER; however when a promoter fragment containing all three sequences was used, specific, high-affinity ER-DNA interactions were observed. It was not surprising, therefore, that, when assayed individually on a heterologous promoter, these sequences function as weak EREs but together they act in a synergistic manner to create a strong ER-dependent enh...Continue Reading

Citations

Jul 14, 2001·Nucleic Acids Research·C M Klinge
Jul 25, 2012·Molecular and Cellular Biology·Khalid HilmiSylvie Mader
Jan 1, 1997·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·D P McDonnell, J D Norris
Feb 7, 2001·Trends in Endocrinology and Metabolism : TEM·D P McDonnell
Feb 24, 2016·Life·Tamara Fernández-CaleroMónica Marín
Sep 23, 2008·Biochimica Et Biophysica Acta·Marinella ZilliUNKNOWN Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO)
Aug 2, 2008·Molecular Reproduction and Development·Yin-Lau LeeWilliam S B Yeung
Feb 26, 2011·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·J SalehK Cianflone
Sep 1, 2004·Maturitas·Donald P McDonnell
Sep 24, 2015·Biochemical and Biophysical Research Communications·Per AntonsonKarin Dahlman-Wright
Sep 30, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Georg KretzschmarGünter Vollmer
Sep 29, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Antonio CaldarelliGuenter Vollmer
Mar 13, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Tamara Fernández-CaleroMónica Marin
Jun 21, 2011·Marine Pollution Bulletin·Ayako Casanova-NakayamaHelmut Segner
Oct 21, 2016·Hormones and Behavior·Ewa SzwejserMagdalena Chadzinska
Sep 24, 2019·Endocrine Reviews·Elisabetta VegetoAngelo Poletti
Oct 13, 2000·American Journal of Physiology. Cell Physiology·M E NuttallL J Suva
Jan 25, 2002·Annals of the New York Academy of Sciences·D P McDonnellJ D Norris

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.