CpG Methylation Changes G-Quadruplex Structures Derived from Gene Promoters and Interaction with VEGF and SP1
by
Kaori Tsukakoshi 1,†, Shiori Saito 1,†, Wataru Yoshida 2,†, Shinichi Goto 1 and Kazunori Ikebukuro 1,*
Kaori Tsukakoshi 1,†, Shiori Saito 1,†, Wataru Yoshida 2,†, Shinichi Goto 1 and Kazunori Ikebukuro 1,*
1
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan
2
School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakuramachi, Hachioji, Tokyo 192-0982, Japan
*
Author to whom correspondence should be addressed.
â€
These authors contributed equally to this work.
Molecules 2018, 23(4), 944; https://doi.org/10.3390/molecules23040944
Received: 31 March 2018 / Revised: 13 April 2018 / Accepted: 15 April 2018 / Published: 18 April 2018
(This article belongs to the Special Issue Nucleic Acid Aptamers)
G-quadruplex (G4) is a DNA/RNA conformation that consists of two or more G-tetrads resulting from four-guanine bases connected by Hoogsteen-type hydrogen bonds, which is often found in the telomeres of chromatin, as well as in the promoter regions of genes. The function of G4 in the genomic DNA is being elucidated and some G4-protein interactions have been reported; these are believed to play a role in vital cellular functions. In this study, we focused on CpG methylation, a well-known epigenetic modification of the genomic DNA, especially found in the promoter regions. Although many G4-forming sequences within the genomic DNA harbor CpG sites, the relationship between CpG methylation and the binding properties of associated proteins remains unclear. We demonstrated that the binding ability of vascular endothelial growth factor (VEGF) G4 DNA to VEGF165 protein was significantly decreased by CpG methylation. We identified the binding activity of G4 DNA oligonucleotides derived from gene promoter regions to SP1, a transcription factor that interacts with a G4-forming DNA and is also altered by CpG methylation. The effect of methylation on binding affinity was accompanied by changes in G4 structure and/or topology. Therefore, this study suggested that CpG methylation might be involved in protein binding to G4-forming DNA segments for purposes of transcriptional regulation.
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Keywords:
G-quadruplex; CpG methylation; vascular endothelial growth factor; SP1; protein-DNA binding
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MDPI and ACS Style
Tsukakoshi, K.; Saito, S.; Yoshida, W.; Goto, S.; Ikebukuro, K. CpG Methylation Changes G-Quadruplex Structures Derived from Gene Promoters and Interaction with VEGF and SP1. Molecules 2018, 23, 944.
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