G-quadruplex Formation Within the Promoter Region of and Its Effect on Transcription

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Feb 1

PMID 38298658

Authors

Ying Li

Zhichao He

Zewu Li

Yan Lu

Qingqing Xun

Longquan Xiang

Miaomiao Zhang

Affiliations

Soon will be listed here.

Abstract

G-rich sequences in DNA and RNA tend to fold into stable secondary structures called G-quadruplexes. Except for the telomere region, G-quadruplex-forming sequences are widely present in gene promoters and have been implicated in transcriptional regulation. Single nucleotide polymorphisms (SNPs) can disrupt the G-quadruplex structure of a gene promoter. In this study, we confirmed the promoter of HSPB2, a cancer-related gene, tends to form an unusual DNA secondary structure. The dual luciferase assay revealed that the SNP rs2234704 in the promoter with a single G > A mutation increased the transcriptional activity of the promoter. Circular dichroism and native PAGE revealed that the G-rich strand of the DNA in this promoter preferred to form a parallel G-quadruplex, which could be destabilized by the SNP rs2234704 (G > A) mutation. Furthermore, we found that the SNP rs2234704 (G > A) greatly increased and influenced the overexpression of in breast cancer samples. These results suggest SNP rs2234704 (G > A) may play a role in the occurrence of breast cancer by destroying the G-quadruplex structure and promoting the expression of HSPB2.

Citing Articles

Pathogenic SNPs Affect Both RNA and DNA G-Quadruplexes' Responses to Ligands.

Turcotte M, Perreault J ACS Chem Biol. 2024; 19(5):1045-1050.

PMID: 38688038 PMC: 11106744. DOI: 10.1021/acschembio.4c00104.

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