Estradiol-Estrogen Receptor alpha Mediates the Expression of the CXXC5 Gene through the Estrogen Response Element-Dependent Signaling Pathway

Date

2016-11-25

Author

Yasar, Pelin
Ayaz, Gamze
Muyan, Mesut

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

165
views

0
downloads

17 beta-estradiol (E2), the primary circulating estrogen hormone, mediates physiological and pathophysiological functions of breast tissue mainly through estrogen receptor alpha (ER alpha). Upon binding to E2, ER alpha modulates the expression of target genes involved in the regulation of cellular proliferation primarily through interactions with specific DNA sequences, estrogen response elements (EREs). Our previous microarray results suggested that E2-ER alpha modulates CXXC5 expression. Because of the presence of a zinc-finger CXXC domain (ZF-CXXC), CXXC5 is considered to be a member of the ZF-CXXC family, which binds to non-methylated CpG dinucleotides. Although studies are limited, CXXC5 appears to participate as a transcription factor, co-regulator and/or epigenetic factor in the regulation of cellular events induced by various signaling pathways. However, how signaling pathways mediate the expression of CXXC5 is yet unclear. Due to the importance of E2-ER alpha signaling in breast tissue, changes in the CXXC5 transcription/synthesis could participate in E2-mediated cellular events as well. To address these issues, we initially examined the mechanism whereby E2-ER alpha regulates CXXC5 expression. We show here that CXXC5 is an E2-ER alpha responsive gene regulated by the interaction of E2-ER alpha with an ERE present at a region upstream of the initial translation codon of the gene.

Subject Keywords

BREAST-CANCER CELLS, INDUCIBLE NUCLEAR FACTOR, TRANSCRIPTIONAL RESPONSES, MOLECULAR DETERMINANTS, ER-ALPHA, TARGET, DIFFERENTIATION, PROTEINS, BINDING, BETA

URI

https://hdl.handle.net/11511/36882

Journal

SCIENTIFIC REPORTS

DOI

https://doi.org/10.1038/srep37808

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

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 ...
Functional importance of CXXC5 in E2-driven cellular proliferation Razizadeh, Negin; Muyan, Mesut; Department of Biology (2019) 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 ...
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...
Establishment of cell lines with inducible expression OF shRNA for an estrogen responsive gene Karakaya, Burcu; Beklioğlu, Meryem; Department of Biology (2018) 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 ...
Assessment of 17beta-estradiol-estrogen receptor alpha complex-mediated changes in genome-wide methylation and gene expression profiles User, Sırma Damla; Muyan, Mesut; Department of Biology (2016) 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 th...

Citation Formats

P. Yasar, G. Ayaz, and M. Muyan, “Estradiol-Estrogen Receptor alpha Mediates the Expression of the CXXC5 Gene through the Estrogen Response Element-Dependent Signaling Pathway,” SCIENTIFIC REPORTS, pp. 0–0, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/36882.