For decades, researchers believed that the genome’s 3D organization disappears when cells divide, leaving chromosomes in a compact, featureless state. A new study from MIT challenges that assumption, showing that small DNA loops connecting regulatory elements and genes remain intact during mitosis.
Using Region-Capture Micro-C (RC-MC), a mapping method with up to 1,000 times higher resolution than Hi-C, the team visualized fine-scale chromatin interactions that persist through cell division. “In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that’s not quite the case,” said Anders Sejr Hansen, associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”
RC-MC allowed the researchers to observe “microcompartments,” highly connected loops between enhancers and promoters that remain visible, and even strengthen, as chromosomes condense. This finding contrasts sharply with the disappearance of larger features such as A/B compartments and topologically associating domains.
“We went into this study thinking, well, the one thing we know for sure is that there’s no regulatory structure in mitosis, and then we accidentally found structure in mitosis,” Hansen said.
The loops appear to play a role in a brief transcriptional spike that occurs near the end of mitosis. As chromatin compacts, enhancers and promoters are brought into closer proximity, which may trigger transient activation of nearby genes. “It almost seems like this transcriptional spiking in mitosis is an undesirable accident that arises from generating a uniquely favorable environment for microcompartments to form,” Hansen added.
The study reframes how scientists view genome structure through the cell cycle, suggesting that the genome retains a subtle but persistent memory of its regulatory architecture even during division.
Publication Details
Goel, V.Y., Aboreden, N.G., Jusuf, J.M. et al. Dynamics of microcompartment formation at the mitosis-to-G1 transition. Nat Struct Mol Biol (2025). https://doi.org/10.1038/s41594-025-01687-2
Using Region-Capture Micro-C (RC-MC), a mapping method with up to 1,000 times higher resolution than Hi-C, the team visualized fine-scale chromatin interactions that persist through cell division. “In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that’s not quite the case,” said Anders Sejr Hansen, associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”
RC-MC allowed the researchers to observe “microcompartments,” highly connected loops between enhancers and promoters that remain visible, and even strengthen, as chromosomes condense. This finding contrasts sharply with the disappearance of larger features such as A/B compartments and topologically associating domains.
“We went into this study thinking, well, the one thing we know for sure is that there’s no regulatory structure in mitosis, and then we accidentally found structure in mitosis,” Hansen said.
The loops appear to play a role in a brief transcriptional spike that occurs near the end of mitosis. As chromatin compacts, enhancers and promoters are brought into closer proximity, which may trigger transient activation of nearby genes. “It almost seems like this transcriptional spiking in mitosis is an undesirable accident that arises from generating a uniquely favorable environment for microcompartments to form,” Hansen added.
The study reframes how scientists view genome structure through the cell cycle, suggesting that the genome retains a subtle but persistent memory of its regulatory architecture even during division.
Publication Details
Goel, V.Y., Aboreden, N.G., Jusuf, J.M. et al. Dynamics of microcompartment formation at the mitosis-to-G1 transition. Nat Struct Mol Biol (2025). https://doi.org/10.1038/s41594-025-01687-2