Researchers map 50,000 of DNA’s mysterious ‘knots’ widely distributed throughout the human genome

Amazing stuff! I suppose we still do not know much about the function of these DNA i-motif structures.

"DNA is well-known for its double helix shape. But the human genome also contains more than 50,000 unusual ‘knot’-like DNA structures called i-motifs, ...

the first comprehensive map of these unique DNA structures, shedding light on their potential roles in gene regulation involved in disease.

In a landmark 2018 study, ... scientists were the first to directly visualise i-motifs inside living human cells using a new antibody tool they developed to recognise and attach to i-motifs. The current research builds on those findings by deploying this antibody to identify i-motif locations across the entire genome. ...

The researchers found that i-motifs are not randomly scattered but concentrated in key functional areas of the genome, including regions that control 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.  ..."

From the abstract:

"DNA i-motif structures are formed in the nuclei of human cells and are believed to provide critical genomic regulation. While the existence, abundance, and distribution of i-motif structures in human cells has been demonstrated and studied by immunofluorescent staining, and more recently NMR and CUT&Tag, the abundance and distribution of such structures in human genomic DNA have remained unclear. Here we utilise high-affinity i-motif immunoprecipitation followed by sequencing to map i-motifs in the purified genomic DNA of human MCF7, U2OS and HEK293T cells. Validated by biolayer interferometry and circular dichroism spectroscopy, our approach aimed to identify DNA sequences capable of i-motif formation on a genome-wide scale, revealing that such sequences are widely distributed throughout the human genome and are common in genes upregulated in G0/G1 cell cycle phases. Our findings provide experimental evidence for the widespread formation of i-motif structures in human genomic DNA and a foundational resource for future studies of their genomic, structural, and molecular roles."

Researchers map 50,000 of DNA’s mysterious ‘knots’ in the human genome | Garvan Institute of Medical Research "Innovative study of DNA’s hidden structures may open up new approaches for treatment and diagnosis of diseases, including cancer."

Human genomic DNA is widely interspersed with i-motif structures (open access)

Figure 1. Identification of iM structures in human genomic DNA.

The knot-like i-motif structure protruding from DNA’s double helix was mapped in 50,000 locations in the human genome