Assessment of 17beta-estradiol-estrogen receptor alpha complex-mediated changes in genome-wide methylation and gene expression profiles

User, Sırma Damla
17β-estradiol (E2), the most potent estrogen hormone, induces cellular responses primarily through Estrogen Receptor-alpha (ERα), which is a transcription factor. Interfering E2 signaling indicates that E2 is mitogenic for cells, exemplified by MCF7 cells derived from breast adenocarcinoma, synthesizing ERα endogenously. Studies used exogenous expression of ERα in ERα-negative cell lines to examine structural/functional properties of the receptor. What was unexpected from these studies is the observation that E2 treatment represses cellular proliferation. However, mechanism(s) of this paradoxical phenomenon remains unknown. Methylation is an important epigenetic DNA modification. Changes in methylation alter gene expressions critical for cellular proliferation/differentiation, embryonic development, genomic imprinting and cancer. We therefore hypothesize that distinct methylation statuses of responsive genes’ regulatory regions underlie differential gene expressions, and hence, proliferative and anti-proliferative effects of E2 in cell models. To test this prediction, we generated a cell model stably expressing ERα in MDAMB231 breast cancer cell line. Of the monoclones synthesizing ERα, the MDA-ERα5, based on expected ERα functions, was selected as the cell model to comparatively assess the E2 effects on changes in methylome and transcriptome profiles to those observed in MCF7 cells. Our studies suggest that cell models have cell-specific methylation patterns for the same genomic region at which E2 induces distinct alterations and differentially modulates gene expressions. However, due to the existence of variations among experimental replicates, establishing a correlation between the methylation statuses to gene expression profile of cell lines appears to be immature. An increase in sample size could circumvent this issue.


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Estrogen hormones, primarily 17β-estradiol (E2) as the primary circulating estrogen, are involved in the homeodynamic regulation of various tissues/organs including mammary gland within which estrogen receptor α (ERα) conveys E2 signaling. The binding of E2 to ERα activates the receptor to regulate estrogen responsive gene expressions. Previous microarray and gene expression studies of our laboratory indicate that CXXC5 is an estrogen responsive gene regulated by ERα. Our ongoing studies also indicate that ...
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 ...
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17β-estradiol (E2) as the main circulating estrogen hormone has an important role in the regulation of various tissues including mammary tissue. E2 effects target tissue functions by binding to the nuclear receptors, ERα and β. ERs regulate the expression of target genes. Previous studies conducted in our laboratory indicate that one of these estrogen responsive genes is CXXC5 which is regulated by ERα. CXXC5 has a highly conserved zinc-finger CXXC domain, which makes it a member of zinc-finger CXXC domain ...
Epigenetic characterization of CXXC5 gene locus
Kars, Gizem; Muyan, Mesut; Department of Molecular Biology and Genetics (2018)
17β-estradiol (E2), the main circulating form of estrogen, induces diverse cellular responses through Estrogen Receptor α and β (ERα and ER β). E2 signaling mediates physiology and pathophysiology of several tissues by regulating E2 responsive genes. Previous studies of our laboratory described a noval E2 responsive gene, CXXC5 that is regulated through ERα. CXXC5 is a member of Zinc Finger CXXC domain protein family. Like other members of family, CXXC5 appears to function as epigenetic factor, co-regulator...
Initial characterization of CXXC5 as a putative DNA binding protein
Yaşar, Pelin; Muyan, Mesut; Department of Biology (2015)
17β-estradiol (E2), the main circulating estrogen hormone, is involved in the physiological and pathophysiological regulation of various tissue notably mammary tissue functions. E2 is responsible for the cellular proliferation, differentiation and/or death in target tissue. The E2 effect is mediated by the nuclear receptors, estrogen receptor α and β, as ligand-dependent transcription factors. Upon binding of E2, ER is converted to an active form and regulates the expression of target genes primarily throug...
Citation Formats
S. D. User, “Assessment of 17beta-estradiol-estrogen receptor alpha complex-mediated changes in genome-wide methylation and gene expression profiles,” M.S. - Master of Science, Middle East Technical University, 2016.