Functional importance of CXXC5 in E2-driven cellular proliferation

Download

index.pdf

Date

2019

Author

Razizadeh, Negin

Metadata

Show full item record

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

Item Usage Stats

311
views

103
downloads

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 protein family. The family binds to non-methylated CpG dinucleotides, specifically in CpG island promoters and alters gene expressions through their enzymatic activities for DNA methylation or epigenetic modifications. However, structural and functional properties of CXXC5 remains largely unknown. In an attempt to decipher the role of CXXC5 in E2-ERα mediated cellular events, we uncovered that CXXC5 do not have an intrinsic transcription activation or repression function but through binding to CpG dinucleotides regulates gene expressions distinctly and mutually modulated by E2 as well. This results in E2-driven cellular proliferation. We therefore suggest that CXXC5 as a CpG binder involves in the regulation of E2-mediated transcriptional activation or repression of genes culminating in the regulation of cellular proliferation.

Subject Keywords

Estrogen, Estrogen Receptors., Estrogen, Estrogen Receptor, CXXC5.

URI

http://etd.lib.metu.edu.tr/upload/12623815/index.pdf
https://hdl.handle.net/11511/45490

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

CELL CYCLE-DEPENDENT REGULATION OF CXXC5 SYNTHESIS 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 ...
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 ...
Structural and functional characterization of the CXXC-type zinc finger protein 5 (CXXC5) Ayaz Şen, Gamze; Muyan, Mesut; Department of Biology (2018) Estrogen hormones, particularly 17β-estradiol (E2), are involved in the regulation of physiological and pathophysiological functions of many organs and tissues including breast tissue. The expression of CXXC type zinc finger protein 5 (CXXC5) gene is regulated by E2 through estrogen receptor α. Due to a highly conserved zinc-finger CXXC domain (ZF-CXXC), CXXC5 is considered to be a member of ZF-CXXC family, which binds to non-methylated CpG dinucleotides of transcriptionally active DNA regions. This binding...
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...
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

N. Razizadeh, “Functional importance of CXXC5 in E2-driven cellular proliferation,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Biology., Middle East Technical University, 2019.