Mithilfe einer neuen hochauflösenden Kartierungstechnik finden Wissenschaftler winzige Schleifen im Genom sich teilender Zellen | Dynamik der Mikrokompartimentbildung beim Übergang von Mitose zu G1

Highlight from the press release:

>Before cells can divide, they first need to replicate all of their chromosomes, so that each of the daughter cells can receive a full set of genetic material. Until now, scientists had believed that as division occurs, the genome loses the distinctive 3D internal structure that it typically forms.
>
>Once division is complete, it was thought, the genome gradually regains that complex, globular structure, which plays an essential role in controlling which genes are turned on in a given cell.
>
>However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis.
>
>“This study really helps to clarify how we should think about mitosis. 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,” says Anders Sejr Hansen, an associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”
>
>The researchers also discovered that these regulatory loops appear to strengthen when chromosomes become more compact in preparation for cell division. This compaction brings genetic regulatory elements closer together and encourages them to stick together. This may help cells “remember” interactions present in one cell cycle and carry it to the next one.
>
>“The findings help to bridge the structure of the genome to its function in managing how genes are turned on and off, which has been an outstanding challenge in the field for decades,” says Viraat Goel PhD ’25, the lead author of the study.
>
>…
>
>The findings may offer an explanation for a spike in gene transcription that usually occurs near the end of mitosis, the researchers say. Since the 1960s, it had been thought that transcription ceased completely during mitosis, but in 2016 and 2017, a few studies showed that cells undergo a brief spike of transcription, which is quickly suppressed until the cell finishes dividing.
>
>In their new study, the MIT team found that during mitosis, microcompartments are more likely to be found near the genes that spike during cell division. They also discovered that these loops appear to form as a result of the genome compaction that occurs during mitosis. This compaction brings enhancers and promoters closer together, allowing them to stick together to form microcompartments.
>
>Once formed, the loops that constitute microcompartments may activate gene transcription somewhat by accident, which is then shut off by the cell. When the cell finishes dividing, entering a state known as G1, many of these small loops become weaker or disappear.
>
>“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 during mitosis,” Hansen says. “Then, the cell quickly prunes and filters many of those loops out when it enters G1.”

—

Journal link:

[Dynamics of microcompartment formation at the mitosis-to-G1 transition](https://www.nature.com/articles/s41594-025-01687-2)

Abstract:

>As cells exit mitosis and enter G1, chromosomes decompact and transcription is reestablished. Hi-C studies have indicated that all interphase three-dimensional genome features, including A/B compartments, topologically associating domains and CCCTC-binding factor loops, are lost during mitosis. However, Hi-C is insensitive to features such as microcompartments, nested focal interactions between cis-regulatory elements. Here we apply region capture Micro-C to mouse erythroblasts from mitosis to G1. We unexpectedly observe microcompartments in prometaphase, which strengthen in anaphase and telophase before weakening throughout G1. Microcompartment anchors coincide with transcriptionally spiking promoters during mitosis. Loss of condensin loop extrusion differentially impacts microcompartments and A/B compartments, suggesting that they are partially distinct. Polymer modeling shows that microcompartment formation is favored by chromatin compaction and disfavored by loop extrusion, providing a basis for strong microcompartmentalization in anaphase and telophase. Our results suggest that compaction and homotypic affinity drive microcompartment formation, which may explain transient transcriptional spiking at mitotic exit.