G-quadruplex formation within the promoter region of HSPB2 and its effect on transcription
Ying Li,
Zhichao He,
Zewu Li,
Yan Lu,
Qingqing Xun,
Longquan Xiang,
Miaomiao Zhang
Affiliations
Ying Li
Medical Research Center, Affiliated Hospital of Jining Medical University, Jing Medical University, Jining, Shandong, 272000, PR China
Zhichao He
Medical Equipment Department, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272000, PR China
Zewu Li
Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272000, PR China
Yan Lu
Clinical Laboratory Medicine Department, Jining No.1 People's Hospital, Jining, Shandong, 272000, PR China
Qingqing Xun
School of Clinical Medicine, Jining Medical University, Jining, Shandong, 272000, PR China
Longquan Xiang
Department of Pathology, Jining No.1 People's Hospital, Jining, Shandong, 272000, PR China; Corresponding author.
Miaomiao Zhang
Medical Research Center, Affiliated Hospital of Jining Medical University, Jing Medical University, Jining, Shandong, 272000, PR China; Department of Pathology, Jining No.1 People's Hospital, Jining, Shandong, 272000, PR China; Corresponding author. Medical Research Center, Affiliated Hospital of Jining Medical University, Jing Medical University, Jining, Shandong, 272000, PR China.
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 HSPB2 promoter with a single G > A mutation increased the transcriptional activity of the HSPB2 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 HSPB2 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.
