On Dec. 22, 2025, scientists at Northwestern University announced a landmark effort to understand how the physical structure of our DNA influences human biology, and the 4D Nucleome Project have unveiled the most detailed maps to date of the genome’s three‑dimensional organization across time and space, according to a new study published in Nature.

The findings, generated using human embryonic stem cells and fibroblasts, offer a sweeping view of how genes interact, fold and reposition themselves as cells function and divide, said Feng Yue, PhD, the Duane and Susan Burnham Professor of Molecular Medicine in the Department of Biochemistry and Molecular Genetics, who was a co-corresponding author of the study.

Rather than existing as a straight ladder of code, the human genome folds into looping structures and compartments within the nucleus. These physical interactions can determine which genes turn on or off, influencing everything from development to cell identity and disease.

To study this complexity, Yue and his international collaborators employed a wide array of genomic technologies on fibroblasts and human embryonic stem cells to produce a unified dataset.

This effort identified:

• More than 140,000 chromatin loops per cell type, identifying the underlying elements at the different types of loop anchors and how they contribute to gene regulation.
• Comprehensive classifications of chromosomal domains, including where they reside inside the nucleus.
• High‑resolution 3D models of entire genomes at the single‑cell level, showing how each gene is positioned relative to its neighbors and regulatory elements.

The work underscores a growing recognition that the genome’s function cannot be understood only by reading its sequence and that it’s shape matters, too. By revealing the connections between DNA folding, chromatin loops, gene activity and cell behavior, the study moves the field closer to a holistic view of how genetic instructions operate inside living cells.

Moving forward, Yue said he hopes these tools will eventually help decode how genome misfolding contributes to cancers, developmental disorders and other conditions, opening the door to structural genomics–based diagnostics and therapies.