G4-DNA formation and chromatin remodelling are interdependent in human cells.

Autor:	Lawler NB; School of Molecular Sciences, The University of Western Australia Perth WA Australia cameron.evans@uwa.edu.au swaminatha.iyer@uwa.edu.au nicole.smith@uwa.edu.au.; School of Physics, Mathematics and Computing, The University of Western Australia Perth WA Australia., Ou A; School of Molecular Sciences, The University of Western Australia Perth WA Australia cameron.evans@uwa.edu.au swaminatha.iyer@uwa.edu.au nicole.smith@uwa.edu.au., King JJ; School of Molecular Sciences, The University of Western Australia Perth WA Australia cameron.evans@uwa.edu.au swaminatha.iyer@uwa.edu.au nicole.smith@uwa.edu.au., Evans CW; School of Molecular Sciences, The University of Western Australia Perth WA Australia cameron.evans@uwa.edu.au swaminatha.iyer@uwa.edu.au nicole.smith@uwa.edu.au., Iyer KS; School of Molecular Sciences, The University of Western Australia Perth WA Australia cameron.evans@uwa.edu.au swaminatha.iyer@uwa.edu.au nicole.smith@uwa.edu.au., Smith NM; School of Molecular Sciences, The University of Western Australia Perth WA Australia cameron.evans@uwa.edu.au swaminatha.iyer@uwa.edu.au nicole.smith@uwa.edu.au.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2023 Jun 27; Vol. 14 (28), pp. 7681-7687. Date of Electronic Publication: 2023 Jun 27 (Print Publication: 2023).
DOI:	10.1039/d3sc02533k
Abstrakt:	DNA G-quadruplexes (G4s) have been identified as important biological targets for transcriptional, translational, and epigenetic regulation. The stabilisation of G4s with small molecule ligands has emerged as a technique to regulate gene expression and as a potential therapeutic approach for human diseases. Here, we demonstrate that ligand stabilisation of G4s causes altered chromatin accessibility dependent on the targeting specificity of the molecule. In particular, stabilisation of a target G4 using the highly specific GTC365 ligand resulted in differential accessibility of 61 genomic regions, while the broad-targeting G4 ligand, GQC-05, stabilised many G4s and induced a global shift towards increased accessibility of gene promoter regions. Interestingly, while we observed distinct effects of each ligand on RNA expression levels and the induction of DNA double-stranded breaks, both ligands modified DNA damage response pathways. Our work represents the dual possibility of G4-stabilising ligands for specific or global chromatin modulation via unique targeting characteristics. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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