Side-by-side comparison of G-quadruplex (G4) capture efficiency of the antibody BG4 versus the small-molecule ligands TASQs

Feng, Yilong; He, Zexue; Luo, Zhenyu; Sperti, Francesco Rota; Valverde, Ibai E.; Zhang, Wenli; Monchaud, David

doi:10.1016/j.isci.2023.106846

Cited by 11 publications

(8 citation statements)

References 63 publications

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“…Here, we have not even confirmed the sequence selectivity of the pulldown ability of this ligand. Recently, the localization of G4 and the binding sites of G4-ligand have been detected genome-wide using NGS, suggesting the influence of small molecules on G4 formation under in vivo conditions [ 17 , 18 ]. In the future, it will be important to investigate the effects of various ligands, including the ligand developed in this study, on G4 formation in the drug design of G4-binding drugs.…”

Section: Discussionmentioning

confidence: 99%

Biotinylated cyclic naphthalene diimide as a searching tool for G4 sites on the genome

Fujii,

Sato,

Hidaka

et al. 2024

ANAL. SCI.

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A biotinyl cyclic naphthalene diimide (biotinyl cNDI) (1), in which biotin is introduced on the cyclic linker chain of cNDI with high G-quadruplex (G4) specificity, was synthesized. 1 was used for binding analysis to G4 DNAs such as c-myc, c-kit, CEGF, or TA-core. The results showed that 1 bind to G4 DNAs with high affinity and, especially, two molecules of 1 bind to c-myc DNA from top and bottom of G4 site at K = 3.9 × 10−6 M−1 without changing the G4 structure. As a pulldown assay, 1 and streptavidin magnetic beads could be used to recover a c-myc DNA or 120-mer DNA fragment having single c-myc sequence. The qPCR results for the 120-meric DNAs showed that more than 50% of genomic DNA fragments could be recovered by this pulldown assay. The results obtained here might allow the recovery of G4-containing DNA fragments from genomic DNA to analyze the true G4 present in the genome. Graphic abstract

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Section: Discussionmentioning

confidence: 99%

Biotinylated cyclic naphthalene diimide as a searching tool for G4 sites on the genome

Fujii,

Sato,

Hidaka

et al. 2024

ANAL. SCI.

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“…43,44 However, the applications we developed with the clickable TASQs say much about how likely they are to become important companions for deciphering G4 biology. First, the click chemo-precipitation of G4s (G4-click-CP) helps assess whether suspected G4-forming sequences (both DNA and RNA) do actually fold into G4 structures in cells (G4RP 22 and G4DP 45 protocols, respectively). It also helps determine the extent to which G4 landscapes are modulated in cells by external effectors ( e.g.…”

Section: Discussionmentioning

confidence: 99%

The multivalent G-quadruplex (G4)-ligands MultiTASQs allow for versatile click chemistry-based investigations

et al. 2023

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“…Computational prediction , and a G4-sensitive DNA sequencing approach have suggested the potential for folded G4 structures to form at hundreds of thousands of sites in the human genome. Methods developed to detect G4 structures in cellular chromatin have observed only thousands of G4 structures in human cells, − suggesting that chromatin context suppresses the folding of most G4 structures. Computational prediction, sequencing experiments, and chromatin mapping approaches all show the enrichment of G4s immediately before the transcription start site (TSS) of many protein coding genes in gene regulatory regions called promoters. ,, …”

Section: Introductionmentioning

confidence: 99%

An Upstream G-Quadruplex DNA Structure Can Stimulate Gene Transcription

Chen,

Simeone,

Melidis

et al. 2024

ACS Chem. Biol.

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Four-stranded G-quadruplexes (G4s) are DNA secondary structures that can form in the human genome. G4 structures have been detected in gene promoters and are associated with transcriptionally active chromatin and the recruitment of transcription factors and chromatin remodelers. We adopted a controlled, synthetic biology approach to understand how G4s can influence transcription. We stably integrated G4-forming sequences into the promoter of a synthetic reporter gene and inserted these into the genome of human cells. The integrated G4 sequences were shown to fold into a G4 structure within a cellular genomic context. We demonstrate that G4 structure formation within a gene promoter stimulates transcription compared to the corresponding G4-negative control promoter in a way that is not dependent on primary sequence or inherent G-richness. Systematic variation in the stability of folded G4s showed that in this system, transcriptional levels increased with higher stability of the G4 structure. By creating and manipulating a chromosomally integrated synthetic promoter, we have shown that G4 structure formation in a defined gene promoter can cause gene transcription to increase, which aligns with earlier observational correlations reported in the literature linking G4s to active transcription.

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Side-by-side comparison of G-quadruplex (G4) capture efficiency of the antibody BG4 versus the small-molecule ligands TASQs

Cited by 11 publications

References 63 publications

Biotinylated cyclic naphthalene diimide as a searching tool for G4 sites on the genome

Biotinylated cyclic naphthalene diimide as a searching tool for G4 sites on the genome

The multivalent G-quadruplex (G4)-ligands MultiTASQs allow for versatile click chemistry-based investigations

An Upstream G-Quadruplex DNA Structure Can Stimulate Gene Transcription

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