Characterization of G-quadruplex formation in the ARID1A promoter.
|
| Abstract |
As a member of the SWI/SNF family, ARID1A plays an essential role in modulating chromatin structure and gene expression. The tumor suppressive function of ARID1A has been well-defined and its downregulation in cancers is attributed to genomic deletion, DNA methylation and microRNA-mediated inhibition. In this study, we demonstrated that the negative strand of a C-rich region in the upstream vicinity of the human ARID1A transcription start site could form G-quadruplexes. Synthesized oligonucleotides based on the sequence of this region exhibited molar ellipticity at specific wavelengths characteristic of G-quadruplex structures in circular dichroism analyses. The formation of G-quadruplexes by these oligonucleotides were also proved by native polyacrylamide gel electrophoresis, DNA synthesis block assays, immunofluorescent staining and dimethyl sulfate footprinting studies. In reporter assays, mutations of the G-quadruplex forming sequence reduced ARID1A promoter-mediated transcription. Transfection of the oligonucleotide with the full length of G-quadruplex motif region, but not its partial sequences or the mutants, could both promote endogenous ARID1A expression and reduce cell proliferation.
|
|---|---|
| Authors | Ting Yan, Bo Zhao, Qiong Wu, Wenmeng Wang, Jinming Shi, Dangdang Li, Daniel B Stovall, Guangchao Sui |
| Journal | International journal of biological macromolecules (Int J Biol Macromol) Vol. 147 Pg. 750-761 (Mar 15 2020) ISSN: 1879-0003 [Electronic] Netherlands |
| PMID | 31982538 (Publication Type: Journal Article) |
| Copyright | Copyright © 2020 Elsevier B.V. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!