ArticleLife science alliance2023
Z-flipon variants reveal the many roles of Z-DNA and Z-RNA in health and disease.
Article in Life science alliance, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Z-DNA-induced genomic instability in the human pangenome.Research square · 2026Article
- Biofilm-derived curli and Z-DNA shape anti-DNA antibody responses during Salmonella infections.PLoS pathogens · 2026Article
- MACRO-MOLECULAR CROWDING FAVORS WRITHE IN UNWOUND DNA.bioRxiv : the preprint server for biology · 2026Article
- Alexidine, identified as a Z-DNA inducer by the NanoZ screening platform, acts as a transcriptional regulator.Nucleic acids research · 2026Article
- Non-B DNA structures and their contributions to genetic diversity, aging, and disease.Nucleic acids research · 2026Review
- The Chromaverse Is Colored by Triplexes Formed Through the Interactions of Noncoding RNAs with HNPRNPU, TP53, AGO, REL Proteins, Intrinsically-Disordered Regions, and Flipons.International journal of molecular sciences · 2026Article
- Characterization of Z-DNA dynamics across the tree of life.bioRxiv : the preprint server for biology · 2025Article
- Control of Gene Expression by Proteins That Bind Many Alternative Nucleic Acid Structures Through the Same Domain.International journal of molecular sciences · 2025Article
- Z-DNA Hunter tool for straightforward detection of Z-DNA forming regions and a case study inNAR genomics and bioinformatics · 2025Article
- Z-GENIE: a user-friendly R/Shiny resource for predicting Z-DNA forming regions in DNA.BMC genomics · 2025Article
- GQ-DNABERT reveals GQ proximal enhancer-promoter interactions associated with tissue-specific transcription.Nucleic acids research · 2025Article
- The evolutionary entanglement of flipons with zinc fingers and retroelements has engendered a large family of Z-DNA and G-quadruplex binding proteins.Open biology · 2025Article
- ZSeeker: an optimized algorithm for Z-DNA detection in genomic sequences.Briefings in bioinformatics · 2025Article
- Kolmogorov-Arnold networks for genomic tasks.Briefings in bioinformatics · 2025Article
- Flipons enable genomes to learn by intermediating the exchange of energy for information.Journal of the Royal Society, Interface · 2025Review
- Benchmarking DNA large language models on quadruplexes.Computational and structural biotechnology journal · 2025Article
- Z-DNA formation in promoters conserved between human and mouse are associated with increased transcription reinitiation rates.Scientific reports · 2024Article
- The ancient Z-DNA and Z-RNA specific Zα fold has evolved modern roles in immunity and transcription through the natural selection of flipons.Royal Society open science · 2024Article
- Article
- Neurodegenerative diseases reflect the reciprocal roles played by retroelements in regulating memory and immunity.Frontiers in neuroscience · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identifying roles for Z-DNA remains challenging given their dynamic nature. Here, we perform genome-wide interrogation with the DNABERT transformer algorithm trained on experimentally identified Z-DNA forming sequences (Z-flipons). The algorithm yields large performance enhancements (F1 = 0.83) over existing approaches and implements computational mutagenesis to assess the effects of base substitution on Z-DNA formation. We show Z-flipons are enriched in promoters and telomeres, overlapping quantitative trait loci for RNA expression, RNA editing, splicing, and disease-associated variants. We cross-validate across a number of orthogonal databases and define BZ junction motifs. Surprisingly, many effects we delineate are likely mediated through Z-RNA formation. A shared Z-RNA motif is identified in SCARF2, SMAD1, and CACNA1 transcripts, whereas other motifs are present in noncoding RNAs. We provide evidence for a Z-RNA fold that promotes adaptive immunity through alternative splicing of KRAB domain zinc finger proteins. An analysis of OMIM and presumptive gnomAD loss-of-function datasets reveals an overlap of Z-flipons with disease-causing variants in 8.6% and 2.9% of Mendelian disease genes, respectively, greatly extending the range of phenotypes mapped to Z-flipons.
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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.