Novel estrogen response elements identified by genetic selection in yeast are differentially responsive to estrogens and antiestrogens in mammalian cells.
TLDR
The results of these studies reveal that sequences that bind weakly to hER in vitro are fully functional as EREs in yeast and are conditionally responsive to estrogen in mammalian cells.Abstract:
A powerful and versatile system for the identification of novel response elements for members of the intracellular receptor family is presented as applied to the human estrogen receptor. In the past, a limited number of estrogen response elements (EREs) have been functionally identified in the promoter regions of estrogen-regulated genes. From these a consensus ERE has been defined that is identical to the ERE of the Xenopus laevis vitellogenin gene, i.e., 5'-GGTCA NNN TGACC-3'. In order to investigate without bias the range of sequences that could function as EREs in vivo, we have developed a genetic selection in yeast expressing the human estrogen receptor (hER) and transformed with a random oligonucleotide library in a vector where expression of a selectable marker requires insertion of an upstream activating sequence. More than 1,000,000 transformants were screened and of 726 clones that contained activating sequences, 65 were found to be hormone-dependent. Sequencing revealed that the majority contai...read more
Citations
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Estrogen receptor interaction with estrogen response elements.
TL;DR: Review of data from the own laboratory and those in the literature indicate that ERalpha binding affinity does not relate linearly with E(2)-induced transcriptional activation, and it is suggested that the reasons for this discord include cellular amounts of coactivators and adaptor proteins that play roles both in ER binding and transcriptionalactivation; phosphorylation of ER and other proteins involved in transcriptional activated; and sequence-specific and protein-induced alterations in chromatin architecture.
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Basic Guide to the Mechanisms of Antiestrogen Action
TL;DR: The identification of the target site-specific actions of tamoxifen caused a paradigm shift in the prospective uses of antiestrogens from a direct exploitation of the antitumor properties to the broader application as a preventative for osteoporosis, but with the beneficial side effects of preventing breast and endometrial cancer.
Journal ArticleDOI
Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha.
TL;DR: The cloning of the cDNA encoding the mouse homolog of estrogen receptor-beta (ER beta) and the functional characterization of mouse ER beta protein suggest the existence of two previously unrecognized pathways of estrogen signaling; I, via ER beta in cells exclusively expressing this subtype, and II, via the formation of heterodimers in cells expressing both receptor subtypes.
Journal ArticleDOI
The Human Estrogen Receptor-α Is a Ubiquitinated Protein Whose Stability Is Affected Differentially by Agonists, Antagonists, and Selective Estrogen Receptor Modulators
TL;DR: It is concluded that the different conformational states adopted by ERα in the presence of different ligands influence transcriptional activity directly by regulating cofactor binding and indirectly by modulating receptor stability.
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