DNA is famous for its double helix shape. However, researchers at the Garvan Institute have found over 50,000 unusual “knots”-like structures called i-motifs in the human genome. Published in The EMBO Journal, this is the first complete map of these DNA structures, which may play a role in gene regulation and disease.
Garvan scientists first visualized i-motifs in human cells in 2018 using a particular antibody, which they now use to find i-motifs throughout the entire genome.
Professor Daniel Christ from the Garvan Institute, “We found over 50,000 i-motif sites in the human genome across all three cell types we studied. This high number shows that i-motifs are common and probably important for how genes function.”
Unlike the usual double helix, i-motifs are four-stranded DNA structures formed by cytosine pairing on the same strand. The study found that these i-motifs are not randomly located but are mainly found in essential areas of the genome that control gene activity.
Cristian David Peña Martinez, the study’s first author, said, “We found that i-motifs are linked to genes that are very active at certain times in the cell cycle, suggesting they help regulate gene activity. “We also discovered i-motifs in the promoter region of oncogenes like the MYC oncogene, offering a chance to target disease-related genes through the i-motif structure.”
The widespread presence of i-motifs near key sequences linked to hard-to-treat cancers offers new opportunities for diagnostics and treatments. This could design drugs targeting i-motifs to affect gene expression. Professor Christ adds that this discovery was possible due to Garvan’s expertise in antibody development and genomics.
Journal reference:
- Cristian David Peña Martinez, Mahdi Zeraati, et al., Human genomic DNA is widely interspersed with i-motif structures. The EMBO Journal. DOI:10.1038/s44318-024-00210-5.