A future phase aims to combine genomic datasets with advanced imaging to study nuclear changes during development and disease, expanding understanding of genome architecture and gene function.

The results provide unprecedented detail on how genome structure correlates with gene expression and cellular function.

The work is NIH Common Fund–funded under the 4D Nucleome Project and was published in Nature on December 17, 2025, with related studies available on Nature’s collection site.

Key insights link chromosome folding and nuclear positioning to transcription and replication, noting cell-to-cell variation and changes during development or stress.

The study integrates data from multiple technologies—Hi-C, micro-C, SPRITE, ChiA-Pet, PLAC-seq, GAM—and from many labs across eight countries to map genome folding and its variation.

The study reveals dynamic genomic folding with more than 140,000 looping interactions between genes and long-range regulatory elements across the cell types studied.

This integrative approach demonstrates how combining datasets allows dynamic modeling of genome function and assigning roles to regulatory elements and genes within a 3D context.

A large international collaboration led by a prominent genome architect mapped the three-dimensional folding of the human genome over time in human embryonic stem cells and immortalized fibroblasts, producing the most detailed 4D view to date.

The findings are published in Nature, contributing to the understanding of genome organization and its functional implications.

Researchers provide a scientific user’s guide in the form of a table and decision tree detailing the strengths and contributions of each experimental technique to help researchers choose methods for questions about three-dimensional genome organization.

The project shows how diverse data can train deep learning models to screen DNA sequences and uncover mechanisms of genome folding and gene function, enabling predictive analyses.

Co-authors include Oliver J. Rando and researchers from UMass Chan Medical School and other participating institutions.