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The ligand-mediated nuclear mobility and interaction with estrogen-responsive elements of estrogen receptors are subtype specific
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Date
2012-12-01
Author
Muyan, Mesut
Huang, Yanfang
Lee, Andrew J.
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17 beta-Estradiol (E-2) plays important roles in functions of many tissues. E-2 effects are mediated by estrogen receptor (ER) alpha and beta. ERs regulate transcriptions through estrogen-responsive element (ERE)-dependent and ERE-independent modes of action. ER binding to ERE constitutes the basis of the ERE-dependent pathway. Direct/indirect ER interactions with transcription complexes define ERE-independent signaling. ERs share functional features. Ligand-bound ERs nevertheless induce distinct transcription profiles. Live cell imaging indicates a dynamic nature of gene expressions by highly mobile ERs. However, the relative contribution of ER mobility at the ERE-independent pathway to the overall kinetics of ER mobility remains undefined. We used fluorescent recovery after a photo-bleaching approach to assess the ligand-mediated mobilities of ERE binding-defective ERs, EREBD. The decrease in ER alpha mobility with E-2 or the selective ER modulator 4-hydroxyl-tamoxifen (4HT) was largely due to the interaction of the receptor with ERE. Thus, ER alpha bound to E-2 or 4HT mediates transcriptions from the ERE-independent pathway with remarkably fast kinetics that contributes fractionally to the overall motility of the receptor. The antagonist Imperial Chemical Industries 182 780 immobilized ER alpha s. The mobilities of ER beta and ER beta(EBD) in the presence of ligands were indistinguishable kinetically. Thus, ER beta mobility is independent of the nature of ligands and the mode of interaction with target sites. Chimeric ERs indicated that the carboxyl-termini are critical regions for subtype-specific mobility. Therefore, while ERs are highly mobile molecules interacting with target sites with fast kinetics, an indication of the hit-and-run model of transcription, they differ mechanistically to modulate transcriptions. Journal of Molecular Endocrinology (2012) 49, 249-266
Subject Keywords
Breast-cancer cells
,
Er-alpha
,
Transcriptional responses
,
DNA-binding
,
Signaling pathways
,
Gene-expression
,
Beta
,
Activation
,
Coactivator
,
Recruitment
URI
https://hdl.handle.net/11511/36061
Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
DOI
https://doi.org/10.1530/jme-12-0097
Collections
Department of Biology, Article
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17β-estradiol (E2) is the main estrogen in circulation and has many physiological effects on various tissues, including the mammary tissue. CXXC5 is an estrogen-responsive gene product that binds to nonmethylated CpG dinucleotides on DNA. CXXC5 synthesis shows fluctuation in the cell cycle. This led to our prediction that the level of CXXC5 synthesis is regulated through the cell cycle. To test this prediction, I investigated the synthesis of CXXC5 in cell cycle-synchronized cells for every 6h up to 36h. I ...
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M. Muyan, Y. Huang, and A. J. Lee, “The ligand-mediated nuclear mobility and interaction with estrogen-responsive elements of estrogen receptors are subtype specific,”
JOURNAL OF MOLECULAR ENDOCRINOLOGY
, pp. 249–266, 2012, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/36061.