DNA is famous for its double helix structure, but the human genome also contains more than 50,000 unusual knot-like DNA structures known as i-motifs, according to a team of experts at the Garvan Medical Research Institute.
In a study published in EMBO MagazineScientists have provided the first comprehensive map of these unique DNA structures, shedding light on their potential role in gene regulation, particularly in relation to diseases such as cancer.
Frequency and distribution of i-motifs
“DNA i-motif structures form in the nuclei of human cells and are believed to provide critical genomic regulation,” the study authors noted.
While the presence, abundance and distribution of i-motif structures in human cells has been demonstrated and studied by immunofluorescence staining and recently NMR and CUT&Tag, the abundance and distribution of such structures in human genomic DNA remains unclear.
Characterizing mysterious DNA structures
In 2018, Garvan scientists made the breakthrough of being the first to directly visualize i-motifs in living human cells, as detailed in the journal. nature. The team developed a new antibody tool specifically designed to recognize and bind to i-motifs.
The current research builds on this previous work and uses the same antibody to pinpoint the location of i-motifs throughout the human genome.
In this study, we mapped more than 50,000 i-motif sites in the human genome that are present in all three cell types we examined, said senior author Daniel Crist, head of the Antibody Therapeutics Laboratory and director of the Targeted Center. Treatment in Garvan.
This is an incredibly 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 are widespread—and likely play key roles in genomic function.
I-motifs are not randomly distributed
I-motifs are distinct DNA structures that differ from the well-known double helix. They are formed when cytosine bases on a DNA strand pair with each other, creating a twisted, four-stranded configuration that protrudes from the double helix.
This research showed that i-motifs are not randomly distributed. The experts discovered that they were concentrated in key functional regions of the genome, including regions that control gene activity.
The role of i-motifs in gene activity
Experts determined that the formation of distinct DNA structures is dependent on the cell cycle and pH. Furthermore, we provide evidence that i-motif structures form in regulatory regions of the human genome, including promoters and telomeric regions.
The study’s senior author Cristian David Pena-Martinez, a research officer at the Antibody Therapeutics Laboratory, explained that i-motifs are associated with genes that are highly active at specific times in the cell cycle, suggesting they play a dynamic role in regulating gene activity. they do
We also found that i-motifs form in the promoter region of oncogenes, such as the MYC oncogene, which encodes one of the most notorious cancer targets. This is an exciting opportunity to target disease-related genes through the i-motif structure.
Implications for intractable cancers
According to study co-author Sarah Komerfeld, assistant professor and chief scientific officer at Garvan, the widespread presence of i-motifs near these “holy grail” sequences implicated in hard-to-treat cancers opens up new opportunities for diagnostic and therapeutic approaches. .
“It may be possible to design drugs that target i-motifs to influence gene expression, which could expand current treatment options,” said Professor Kummerfeld.
Importance of study
Professor Crist noted that the successful mapping of i-motifs was made possible by Garvan’s world-leading expertise in antibody development and genomics.
“This study is an example of how basic research and technological innovation can combine to make paradigm-shifting discoveries,” says Professor Crist.
“Our study provides fundamental knowledge and resources regarding the location and distribution of i-motifs in human genomic DNA, indicating potential targets for future diagnostic and therapeutic strategies,” the authors concluded.
—–
Like what you read? Subscribe to our newsletter for interesting articles, exclusive content and latest updates.
Check us out at EarthSnap, a free app brought to you by Eric Rawls and Earth.com.
—–
#DNA #mystery #knots #human #genome