This is no factory to
tinker with. Blind watch-
makers need not apply.

This article was initially published in Science & Culture Today.

4-D Nucleome Mapping Opens
New Vision of Dynamic DNA Architecture
by David Coppedge
Science & Culture Today, January 16, 2026

First, we learned that DNA is a molecule: a nucleic acid. Then we learned that it is a double helix. Then we learned that its 2-D sequence of nucleotides is informational: it codes for genes. Then we learned that DNA is not haphazardly stuffed into the nucleus: it’s a 3-D information system — a genome, with a shape related to its function. Then we learned that the genome is accompanied by a plethora of molecular machines and regulators, comprising an interactome. Then we learned that the shape DNA takes on in the nucleus has an architecture: it folds into topological domains and functional compartments. The interactome became a nucleome.

Now, DNA has entered the fourth dimension: it is a dynamic architecture, constantly reconfiguring itself in functional ways with the aid of a multitude of molecular machines in dizzying motions and interactions. A factory in a cathedral could hardly compare. For the final dose of awe, consider that the molecular machines that operate on DNA are coded in DNA! Gone is the Central Dogma. Gone is the myth of Junk DNA.

This unprecedented expansion of the concept of the “genome” from sequence to dynamic nucleome has been aided by a series of international research programs like ENCODE and its successors. The latest has been the 4D Nucleome Project funded by the NIH Common Fund. A short video from 2023 explains its goals. 

The 4D Nucleome Project (henceforth 4DN) brought together an international consortium of researchers to work on unanswered questions about DNA. They all cooperated in an open-science environment, where data and technologies could be shared through the 4D Nucleome Portal. (See my earlier articles on 4DN from 2017 and 2018.) One might call this an “interactome” of human researchers seeking understanding of the interactome of cellular components.

The 4DN program completed another milestone last month. The findings and techniques perfected so far will continue to bear fruit for years, increasing our understanding of DNA’s dynamic architecture and how diseases result when the architecture breaks down. Feel the excitement of the researchers in this NIH video from summer 2025 describing what they discovered about the nucleome.

Phase One of the 4DN ended in 2020, focusing on developing new technologies for research. Phase Two (2020-2025) ended with a grand finale: an elaborate map of the nucleome presented in Nature. Ninety authors from eight countries contributed to the paper by lead author Job Dekkar of Howard Hughes Medical Institute and corresponding co-author Feng Yue at Northwestern University, “An integrated view of the structure and function of the human 4D nucleome.” The results are impressive….

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