Scientists have produced essentially the most detailed maps yet of how human DNA folds, loops and shifts inside living cells.
- They provide a neat have a look at how genes interact, fold and shift position as cells develop, function and divide.
- Can speed up the invention of disease attributable to genetic mutations and uncover the hidden mechanisms behind inherited disorders
- Researchers hope these tools will eventually reveal how errors in genome folding contribute to cancer, developmental disorders and other diseases.
In a serious step toward understanding how DNA structure shapes human biology, Northwestern University scientists working with the 4D Nucleus Project have produced essentially the most detailed maps yet of how the human genome is organized in three dimensions and the way that organization changes over time. The research, published in , provides a brand new window into how DNA moves inside living cells.
The team created these maps using human embryonic stem cells and fibroblasts. Co-corresponding writer Feng Yu, the Doane and Susan Burnham Professor of Molecular Medicine within the Department of Biochemistry and Molecular Genetics at Northwestern, said the information together provide a comprehensive have a look at how genes interact, associate and shift positions as their normal functions and distributions.
“Understanding how the genome folds and reorganizes in three dimensions is essential to understanding how cells function,” Yu said. “These maps give us an unprecedented view of how genome structure helps regulate gene activity in space and time.”
DNA structure shapes gene activity
DNA doesn’t exist as straight, linear strands inside a cell. Instead, it bends in a loop and forms separate compartments inside the cell nucleus. These physiological arrangements help control which genes are turned on or off, influencing development, cell identity and disease risk.
To capture this complexity, the U and collaborators from all over the world combined quite a lot of advanced genomic techniques. By applying these tools to each fibroblasts and human embryonic stem cells, the researchers assembled a unified and highly detailed dataset that captures genome organization from multiple angles.
What the brand new maps of the genome reveal
The evaluation revealed several major features of genome architecture:
- More than 140,000 chromatin loops in each cell type, with specific elements that anchor these loops and their role in regulating genes
- Detailed classification of chromosomal domains and their positions inside the nucleus
- High-resolution 3D models of your complete genome on the single-cell level, showing how individual genes are arranged relative to nearby genes and regulatory regions.
Together, these findings suggest that genome structure can vary from cell to cell. The differences are closely tied to essential cellular activities akin to transcription and DNA replication.
Evaluating tools for 4D genome studies
Because no experimental method can fully capture the four-dimensional organization of the genome, the researchers also compared the strengths and limitations of the technologies used. Through extensive benchmarking, they identified which approaches work best for detecting, defining domain boundaries, or visualizing subtle changes in DNA status inside the nucleus.
The team also developed computational tools that may predict how a genome will behave based only on its DNA sequence. These tools make it possible to evaluate how genetic mutations—including those related to disease—can alter 3D genome structure without running complex laboratory experiments.
Implications for disease and genetic risk
This capability could speed up the identification of disease-causing mutations and uncover the biological mechanisms behind inherited disorders that were previously difficult to detect, Yu said.
“Since most variants associated with human diseases are located in non-coding regions of the genome, it is important to understand how these variants affect essential gene expression and contribute to disease,” Yu said. “3D genome organization provides a powerful framework for predicting which genes will be affected by these pathogenic variants,” Yu said.
Toward latest diagnostics and coverings
The study reinforces a growing view in genetics that simply reading the DNA sequence shouldn’t be enough. The physical shape of the genome also plays a central role. By linking DNA folding, chromatin loops, gene regulation, and cell behavior, the research brings scientists closer to a more complete understanding of how genetic instructions work inside living cells.
Looking ahead, Yu said he hopes these tools will help researchers uncover how errors in genome folding contribute to cancer, developmental disorders and other diseases, potentially resulting in latest diagnostic strategies and therapeutics based on genome structure.
“Having observed changes in the 3D genome in cancers including leukemia and brain tumors, our next goal is how these structures can be precisely targeted and modulated using drugs such as epigenetic inhibitors,” Yu said.