CXXC5 as an unmethylated CpG dinucleotide binding protein contributes to estrogen-mediated cellular proliferation
Open Access
- 6 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-14
- https://doi.org/10.1038/s41598-020-62912-0
Abstract
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.Keywords
This publication has 74 references indexed in Scilit:
- ZF-CxxC domain-containing proteins, CpG islands and the chromatin connectionBiochemical Society Transactions, 2013
- The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroupsNature, 2012
- A Rapid, Extensive, and Transient Transcriptional Response to Estrogen Signaling in Breast Cancer CellsCell, 2011
- Biological Functions of Methyl-CpG-Binding ProteinsPublished by Elsevier BV ,2011
- A Novel Wilms Tumor 1 (WT1) Target Gene Negatively Regulates the WNT Signaling PathwayPublished by Elsevier BV ,2010
- Genomic Responses from the Estrogen-responsive Element-dependent Signaling Pathway Mediated by Estrogen Receptor α Are Required to Elicit Cellular AlterationsPublished by Elsevier BV ,2009
- The effects of acute 17β-estradiol treatment on gene expression in the young female mouse hippocampusNeurobiology of Learning and Memory, 2009
- Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cellsNucleic Acids Research, 2007
- A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promotersProceedings of the National Academy of Sciences of the United States of America, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001