The ligand-mediated nuclear mobility and interaction with estrogen-responsive elements of estrogen receptors are subtype specific

Muyan, Mesut
Huang, Yanfang
Lee, Andrew J.
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


The regulation of the CXXC5 gene expression
Yaşar, Pelin; Muyan, Mesut; Department of Molecular Biology and Genetics (2021-1-19)
17β-estradiol (E2) is the main circulating estrogen hormone in the body and is involved in the physiological and pathophysiological regulation of various tissue notably mammary tissue functions. E2 is responsible for cellular proliferation, differentiation, and/or death in target tissues. Our previous microarray studies suggested that expression of CXXC5 is regulated by E2-ERα through ERE-dependent signaling pathway and I verified that the CXXC5 transcript levels are augmented in response to E2. As a member...
Molecular mechanism of estrogen-estrogen receptor signaling.
Yaşar, P; Ayaz, G; User, Sd; Güpür, G; Muyan, Mesut (2016-12-05)
17 beta-Estradiol (E2), as the main circulating estrogen hormone, regulates many tissue and organ functions in physiology. The effects of E2 on cells are mediated by the transcription factors and estrogen receptor (ER)alpha and ER beta that are encoded by distinct genes. Localized at the pen-membrane, mitochondria, and the nucleus of cells that are dependent on estrogen target tissues, the ERs share similar, as well as distinct, regulatory potentials. Different intracellular localizations of the ERs result ...
Dynamic transcriptional events mediated by estrogen receptor alpha
Ayaz, Gamze; Yasar, Pelin; Olgun, Çağla Ece; Karakaya, Burcu; Kars, Gizem; Razizadeh, Negin; Yavuzl, Kerim; Turan, Gizem; Muyan, Mesut (Frontiers in Bioscience, 2019-01-01)
17beta-estradiol (E2), the main circulating estrogen hormone, is involved in a wide variety of physiological functions ranging from the development to the maintenance of many tissues and organs. The effects of E2 on cells are primarily conveyed by the transcription factors, estrogen receptor (ER) alpha and beta. The regulation of responsive genes by the well-defined ER alpha in response to E2 relies on complex and highly organized processes that dynamically integrate functions of many transcription regulato...
Cloning and initial protein characterization of an estrogen responsive gene: YPEL2
Güpür, Gizem; Muyan, Mesut; Department of Biology (2014)
17β-estradiol (E2), the main circulating estrogen in the body, is involved in physiological regulation of many tissue and organ functions, including mammary tissue. E2 is also involved in target tissue malignancies. E2 regulates cellular proliferation, differentiation and death in target tissues. The lasting effects of E2 on cells are mediated by estrogen receptor and β that are the products of distinct genes and act as transcription factors. Upon binding to E2, the activated ER regulates the expression of ...
Demiralay, Öykü Deniz; Muyan, Mesut; Department of Biology (2022-8-22)
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 ...
Citation Formats
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: