– A new research-oriented perspective throws light into the mystery of various gene linked diseases
We know that DNA structure is complex. DNA within the cells is not existing as a straight, linear strand. Instead, it bends into loops and forms distinct compartments within the cell nucleus. The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function in a varied way.
A study conducted by a group of researchers in 4D Nucleome Project1 to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts (HFFc6).
The scientists at Northwestern University working with the 4D Nucleome Project have made the most comprehensive maps hitherto available, about the human genome organizing in three dimensions and how that organization changes over time.
The research is published in ‘Nature journal and it opens up new windows in genetics and medical science regarding the DNA operations inside living cells. These maps provide a new outlook of how genome structure helps regulate gene activity.
The study provides details about:
- More than 140,000 chromatin loops in each cell type, along with the specific elements that anchor those loops and their role in regulating genes.
- Detailed classifications of chromosomal domains and their positions within the nucleus.
- High-resolution 3D models of entire genomes at the single-cell level, showing how individual genes are arranged relative to nearby genes and regulatory regions.
Together, these findings show that genome structure can vary from one cell to another. The differences are closely tied to essential cellular activities such as transcription and DNA replication.
According to Science daily the mapping 4D nucleome project provides links between chromosome folding and genomic function ; mechanisms of folding can be explored and causal relationships between genome structure and function can be deduced.
These physical arrangements help control which genes are switched on or off, influencing development, cell identity, and the risk of disease.
The analysis uncovered several major features of genome architecture:
- this has the potential for the identification of disease-causing mutations and unravel the biological mechanisms behind inherited disorders that were previously difficult to detect.
According to the research team the majority of variants associated with human diseases are located in the non-coding regions of the genome, it is critical to understand how these variants influence essential gene expression and contribute to disease.
The 3D genome organization provides a powerful framework for predicting which genes are likely to be affected by these pathogenic variants.
The study breaks the conventions in genetics that reading DNA sequences alone is insufficient. The physical shape of the genome also plays a key role.
By linking DNA folding, chromatin loops, gene regulation, and cell behavior, the research provides a more comprehensive understanding of the cellular genetic mechanism.
This new study outcome will help researchers understand thoroughly how errors in genome folding contribute to cancer, developmental disorders, and other diseases. leading to new diagnostic strategies and therapies based on genome structure.
Written by dr sanjana p
REFERENCE for further reading
An integrated view of the structure and function of the human 4D nucleome. Nature, 2025; DOI: 10.1038/s41586-025-09890-3