A prevailing belief that the 3D structure of DNA disappears completely when cells divide has been overturned. Rather than DNA fully unwinding into a flat configuration, some regions of chromosomes retain a looped three-dimensional structure. The structure is presumed to act like an electric circuit connecting genes and regulatory switches.
Researchers at the Massachusetts Institute of Technology (MIT) said in the international journal Nature Structural & Molecular Biology on Oct. 17 that they had found that fine three-dimensional structures involved in gene regulation still exist in the genome of chromosomes even at the moment cells split.
The genome is in the chromosomes of the cell nucleus. Chromosomes are formed by DNA strands winding around proteins that act like spools. They are 95% water and thus hard to see, but they take dye well, which is why they are called chromosomes.
DNA has a backbone of sugar and phosphate forming a double helix, with the four bases A, G, C, and T paired with their matching bases like a zipper in between. DNA synthesizes proteins according to the order in which these bases are linked, governing life processes. Decoding the genome means determining the DNA base sequence.
Cell division is the process of passing on an identical genome to the next generation. Before division, somatic cells that make up the body must precisely replicate the chromosomes that carry the genome. Only then can the two daughter cells each inherit complete genetic information. Until now, scientists thought the chromosomes' complex 3D architecture collapses during this process and recovers gradually only after division ends.
Using ultra–high-resolution genome analysis, the MIT team captured evidence that small looped 3D structures, called loops, remain even during cell division. While larger-scale chromosome structures were known to disappear completely during division, smaller-unit structures stayed intact.
The team explained that these loops, which persist during cell division, act like electrical circuit lines linking regulatory regions that switch genes on and off with the sites where gene expression begins. Only 2% of the genome consists of genes that actually synthesize proteins. Half of the genome serves to regulate whether these genes are turned on or off. The structure that links genes and regulatory switches in the genome has been identified.
The researchers first discovered in 2023, using high-resolution analysis, loop structures that persist through cell division, and this time they confirmed that they are maintained during division. Anders Sejr Hansen, a professor of biological engineering at MIT, said, "Until now, we regarded cell division as a completely flat state, but in reality the three-dimensional structure does not disappear entirely," adding, "The genome always maintains a certain shape and, if anything, becomes more tightly condensed during division."
The team also suggested the possibility that this phenomenon may relate to how cells maintain memory. It could serve as a kind of "genetic memory device" that passes gene regulatory information from one cell cycle to the next.
The discovery also explains brief gene activity observed at the end of cell division. Previously, transcription—the copying of genetic information—was thought to halt completely during division, but in reality gene expression rises briefly. The team analyzed that as chromosomes compress, regulatory regions and genes come closer, loops form, and as a result some genes can switch on temporarily.
Hansen added, "This appears to be a kind of side effect that cells did not intend," and "Once division ends, cells promptly clear unnecessary loops and restore their original balance."
The researchers plan to explore how cell size and shape affect these changes in genome structure. Hansen said, "How cells decide which loops to maintain and which to eliminate, and how that impacts cell identity and the fidelity of gene expression, will be key research topics going forward."
References
Nature Structural & Molecular Biology (2025), DOI: https://doi.org/10.1038/s41594-025-01687-2
Nature Genetics (2023), DOI: https://doi.org/10.1038/s41588-023-01391-1