CXXC5 as an unmethylated CpG dinucleotide binding protein contributes to estrogen-mediated cellular proliferation.

Download

10.1038:s41598-020-62912-0.pdf

Date

2020-04-06

Author

Ayaz, G
Razizadeh, N
Yaşar, P
Kars, G
Kahraman, Deniz Cansen
Saatci, Ö
Şahin, Ö
Çetin-Atalay, R
Muyan, M

Metadata

Show full item record

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

Item Usage Stats

181
views

122
downloads

Evidence suggests that the CXXC type zinc finger (ZF-CXXC) protein 5 (CXXC5) is a critical regulator/integrator of various signaling pathways that include the estrogen (E2)-estrogen receptor α (ERα). Due to its ZF-CXXC domain, CXXC5 is considered to be a member of the ZF-CXXC family, which binds to unmethylated CpG dinucleotides of DNA and through enzymatic activities for DNA methylation and/or chromatin modifications generates a chromatin state critical for gene expressions. Structural/functional features of CXXC5 remain largely unknown. CXXC5, suggested as transcription and/or epigenetic factor, participates in cellular proliferation, differentiation, and death. To explore the role of CXXC5 in E2-ERα mediated cellular events, we verified by generating a recombinant protein that CXXC5 is indeed an unmethylated CpG binder. We uncovered that CXXC5, although lacks a transcription activation/repression function, participates in E2-driven cellular proliferation by modulating the expression of distinct and mutual genes also regulated by E2. Furthermore, we found that the overexpression of CXXC5, which correlates with mRNA and protein levels of ERα, associates with poor prognosis in ER-positive breast cancer patients. Thus, CXXC5 as an unmethylated CpG binder contributes to E2-mediated gene expressions that result in the regulation of cellular proliferation and may contribute to ER-positive breast cancer progression.

Subject Keywords

BREAST-CANCER CELLS, GENE-EXPRESSION, RECEPTOR-ALPHA, TRANSCRIPTION FACTORS, PROGNOSTIC-FACTOR, DNA METHYLATION, INSIGHTS, RINF, DIFFERENTIATION, REGULATOR

URI

https://hdl.handle.net/11511/30050

Journal

Scientific reports

DOI

https://doi.org/10.1038/s41598-020-62912-0

Collections

Graduate School of Informatics, Article

Suggestions

OpenMETU
Core

CXCL16 influences the nature and specificity of CpG-induced immune activation. Gürsel, Mayda; Mostowski, HS; Klinman, DM (2006-08-01) Unmethylated CpG motifs are present at high frequency in bacterial DNA. They provide a danger signal to the mammalian immune system that triggers a protective immune response characterized by the production of Th1 and proinflammatory cytokines and chemokines. Although the recognition of CpG DNA by B cells and plasmacytoid dendritic cells is mediated by TLR 9, these cell types differ in their ability to bind and respond to structurally distinct classes of CpG oligonucleotides. This work establishes that CXCL...
Expression Analysis of TaNAC69-1 and TtNAMB-2, Wheat NAC Family Transcription Factor Genes Under Abiotic Stress Conditions in Durum Wheat (Triticum turgidum) Baloglu, Mehmet Cengiz; Oz, Mehmet Tufan; Öktem, Hüseyin Avni; Yücel, Ayşe Meral (2012-10-01) NAC-type plant-specific transcription factor genes encode proteins that play important roles in abiotic stress responses, as well as regulation of plant development. In the current study, expression profiles of wheat NAC-type transcription factor genes, TaNAC69-1 and TtNAMB-2, were examined under drought, salt, cold, and heat stress conditions in wheat. Based on reverse transcription quantitative PCR results, TaNAC69-1 was strongly expressed under drought, salinity, and high-temperature stress conditions. C...
Mammalian Telomeric DNA Suppresses Endotoxin-induced Uveitis Yagci, Fuat C.; Aslan, Ozlem; Gürsel, Mayda; Tincer, Gizem; Özdamar, Yasemin; Karatepe, Kutay; Akcali, K. Can; Gursel, Ihsan (American Society for Biochemistry & Molecular Biology (ASBMB), 2010-7-14) Telomeric regions of mammalian chromosomes contain suppressive TTAGGG motifs that inhibit several proinflammatory and Th1-biased immune responses. Synthetic oligodeoxynucleotides (ODN) expressing suppressive motifs can reproduce the down-regulatory activity of mammalian telomeric repeats and have proven effective in the prevention and treatment of several autoimmune and autoinflammatory diseases. Endotoxin-induced uveitis (EIU) is an established animal model of acute ocular inflammation induced by LPS admin...
The yeast Ste2p G protein-coupled receptor dimerizes on the cell plasma membrane Cevheroglu, Orkun; Kumas, Gozde; Hauser, Melinda; Becker, Jeffrey M.; Son, Çağdaş Devrim (2017-05-01) Dimerization of G protein-coupled receptors (GPCR) may play an important role in maturation, internalization, signaling and/or pharmacology of these receptors. However, the location where dimerization occurs is still under debate. In our study, variants of Ste2p, a yeast mating pheromone GPCR, were tagged with split EGFP (enhanced green fluorescent protein) fragments inserted between transmembrane domain seven and the C-terminus or appended to the C-terminus. Bimolecular Fluorescence Complementation (BiFC) ...
Structural characterization of recombinant bovine Go alpha by spectroscopy and homology modeling MEGA TİBER, PINAR; Orun, Oya; Nacar, Cevdet; Sezerman, Ugur Osman; Severcan, Feride; Severcan, Mete; Matagne, Andre; KAN, BEKİ (2011-01-01) Go, a member of heterotrimeric guanine nucleotide-binding proteins, is the most abundant form of G protein in the central and peripheral nervous systems. Go alpha has a significant role in neuronal development and function but its signal transduction mechanism remains to be clarified.

Citation Formats

G. Ayaz et al., “CXXC5 as an unmethylated CpG dinucleotide binding protein contributes to estrogen-mediated cellular proliferation.,” Scientific reports, pp. 5971–5971, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30050.