DNA is usually known for its classic right-handed double helix. But under certain conditions, it can adopt an alternative shape called Z-DNA. This left-handed structure is increasingly linked to gene regulation, chromatin organization, and immune responses. Two recent publications from the NanoPrecMed network put forward important new findings to better understand this unusual DNA.
A fast and user-friendly tool to detect Z-DNA
In a study published in NAR Genomics and Bioinformatics, researchers from Mendel University, Czech Academy of Sciences and Brno University of Technology, together with University of Ostrava and Charité University Hospital introduced Z-DNA Hunter, a web-based tool that enables fast and reliable detection of Z-DNA-forming sequences (ZFS) across the entire genomes. Until now, genome-wide prediction of Z-DNA was often slow or technically demanding. Z-DNA Hunter changes this by offering a simple interface, rapid analysis (even for whole chromosomes), and clear visualization options. Researchers can upload DNA sequences and identify regions that are likely to adopt the left-handed Z-DNA structure within seconds. To demonstrate its potential, the team analyzed the genome of Drosophila melanogaster. They discovered that long Z-DNA-forming regions are strongly enriched on the X chromosome, while they are almost completely absent on the Y chromosome. This difference suggests that Z-DNA is not randomly distributed but associated with active and functionally important genomic regions.
Which proteins interact with Z-DNA?
A second study, published by Michaela Dobrovolná and Vaclav Brazda in Biochemical and Biophysical Research Communications, explored which proteins may interact with Z-DNA in the human genome. Using Z-DNA Hunter predictions, the researchers compared Z-DNA-forming regions with more than 32,000 ChIP-seq datasets from the ChIP-Atlas database. This large-scale analysis identified transcription factors that frequently overlap with Z-DNA-forming regions. Several well-known regulatory proteins showed strong and consistent enrichment at Z-DNA sites. Interestingly, some proteins not previously linked to Z-DNA, such as MCM2 and FOXP1, were also strongly associated with these regions. This suggests that Z-DNA may play a broader role in gene regulation than previously thought.
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