ArticleJournal of the American Chemical Society2014
The dynamic character of the BCL2 promoter i-motif provides a mechanism for modulation of gene expression by compounds that bind selectively to the alternative DNA hairpin structure.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 115 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
115 citing papers in PubMed, 279 citations in OpenAlex.
- Polyamines are i-motif disruptors.Molecular therapy. Nucleic acids · 2026Article
- Article
- QuaDB: A streamlined web tool for identifier-based rapid prediction of putative quadruplex sequences.Human genomics · 2026Article
- DNA secondary structures in BCL2 and MYC elicit activation-induced cytidine deaminase binding and activity.Nucleic acids research · 2026Article
- Nanopore-Based, Real-Time Single-Molecule Probing of i-Motif Structural Dynamics and Targeted PNA Disruption.Nano letters · 2026Article
- In silico mapping of non-canonical DNA structures across the human ribosomal DNA locus.G3 (Bethesda, Md.) · 2026Article
- Mechanistic insights into PCBP1-driven unfolding of selected i-motif DNA at GNature communications · 2026Article
- i-Motif, not G-quadruplex, stability regulates insulin expression.Nucleic acids research · 2026Article
- i-motifs: DNA structures with regulatory functions and therapeutic potential.Einstein (Sao Paulo, Brazil) · 2026Review
- Chemically modified CRISPR-Cas9 enables targeting of individual G-quadruplex and i-motif structures, revealing ligand-dependent transcriptional perturbation.Nature communications · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- PHASE SEPARATION TUNES THE STABILITY AND DYNAMICS OF G-QUADRUPLEX AND I-MOTIF DNA IN THE NUCLEI OF LIVING CELLS.bioRxiv : the preprint server for biology · 2025Article
- Affinity-selected peptide ligands specifically bind i-motif DNA and modulate c-Myc gene expression.Nucleic acids research · 2025Article
- The Effect of 2'F-RNA on I-Motif Structure and Stability.Molecules (Basel, Switzerland) · 2025Article
- Effects of flanking regions on DNA i-motif folding and stability.Nucleic acids research · 2025Article
- The Influence of CG sites on dynamic DNA sequence mutagenesis in the genomic evolution of mammalian lifespan.Nucleic acids research · 2025Article
- Twisting tetraplex DNA: A strand dynamics regulating i-motif function in diverse molecular crowding environments.Nucleic acids research · 2025Article
- G-quadruplex and i-motif DNA structures form in the promoter of the key innate immune adaptorCell reports. Physical science · 2025Article
- Three- and four-stranded nucleic acid structures and their ligands.RSC chemical biology · 2025Review
- i-Motifs as regulatory switches: Mechanisms and implications for gene expression.Molecular therapy. Nucleic acids · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
It is generally accepted that DNA predominantly exists in duplex form in cells. However, under torsional stress imposed by active transcription, DNA can assume nonduplex structures. The BCL2 promoter region forms two different secondary DNA structures on opposite strands called the G-quadruplex and the i-motif. The i-motif is a highly dynamic structure that exists in equilibrium with a flexible hairpin species. Here we identify a pregnanol derivative and a class of piperidine derivatives that differentially modulate gene expression by stabilizing either the i-motif or the flexible hairpin species. Stabilization of the i-motif structure results in significant upregulation of the BCL2 gene and associated protein expression; in contrast, stabilization of the flexible hairpin species lowers BCL2 levels. The BCL2 levels reduced by the hairpin-binding compound led to chemosensitization to etoposide in both in vitro and in vivo models. Furthermore, we show antagonism between the two classes of compounds in solution and in cells. For the first time, our results demonstrate the principle of small molecule targeting of i-motif structures in vitro and in vivo to modulate gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.