DNA is usually considered to have a double helix. But now researchers from the Garvan Institute of Medical Research found out over 50,000 peculiar DNA structures that resemble ‘knots’ in the human genome-shaped structures called i-motifs.
Their findings were published in The EMBO Journal.
A landmark 2018 study, Garvan scientists were the first in the world to directly observe i-motifs inside living human cells using a new antibody tool they had developed, that was able specifically to bind to them. The new work builds on that by using that antibody to map the locations of i-motifs across the whole genome.
In this study, we mapped more than 50,000 i-motif sites in the human genome that occur in all three of the cell types we examined,
That’s a remarkably high number for a DNA structure whose existence in cells was once considered controversial. Our findings confirm that i-motifs are not just laboratory curiosities but widespread – and likely to play key roles in genomic function.
Professor Daniel Christ
I-motifs are a structure of DNA, somehow different from the usual double helix. I-Motifs arise because of the persistence of cytosine nucleotide chains within one strand of the DNA which interact with each other to form a four-stranded helical structure extruded from the double helix.
It was discovered by the researchers that i-motifs are not dispersed randomly but rather are clustered in important functional sections of the genome, such as those that regulate gene activity.
We discovered that i-motifs are associated with genes that are highly active during specific times in the cell cycle. This suggests they play a dynamic role in regulating gene activity,
We also found that i-motifs form in the promoter region of oncogenes, for instance the MYC oncogene, which encodes one of cancer’s most notorious ‘undruggable’ targets. This presents an exciting opportunity to target disease-linked genes through the i-motif structure
Cristian David Peña Martinez
The widespread presence of i-motifs near these ‘holy grail’ sequences involved in hard-to-treat cancers opens up new possibilities for new diagnostic and therapeutic approaches. It might be possible to design drugs that target i-motifs to influence gene expression, which could expand current treatment options.
Sarah Kummerfeld
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This study is an example of how fundamental research and technological innovation can come together to make paradigm-shifting discoveries.
Cristian David Peña Martinez
Source: Garvan Institute of Medical Research
Journal Reference: Peña Martinez, Cristian David et al. “Human genomic DNA is widely interspersed with i-motif structures.” The EMBO journal, 10.1038/s44318-024-00210-5. 29 Aug. 2024, DOI: 10.1038/s44318-024-00210-5.
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