New insight into mitosis: genome structure isn’t erased
For decades, scientists believed that as cells divide, the genome is stripped of its intricate 3D organization and that this structure gradually returns only after mitosis. A groundbreaking MIT study challenges that view by showing that tiny 3D loops, known as microcompartments, persist throughout cell division and even become more pronounced as chromosomes condense.
What are microcompartments and why they matter
Microcompartments are small, highly connected loops that form when regulatory elements such as enhancers touch promoters to boost gene activity. Using Region-Capture Micro-C (RC-MC), a high-resolution genome-mapping technique, the MIT team could observe these loops at a scale far finer than traditional Hi-C methods. The discovery reveals a layer of genome organization that remains operational during mitosis, a phase once thought to be a transcriptional dead zone.
High-resolution discovery changes the mitosis narrative
Hi-C has long been the workhorse for examining 3D genome structure, but its resolution missed many fine-scale interactions. RC-MC, developed to deliver 100- to 1,000-fold higher resolution, turned this on its head. It confirmed the existence of microcompartments during mitosis and showed that larger structures like A/B compartments and topologically associating domains (TADs) disappear as cells prepare to divide, while microcompartments persist or strengthen.
The mechanism behind persistent microcompartments
As chromosomes condense for division, bringing genes and regulatory regions into closer proximity, microcompartments form more readily. This compaction effectively “remembers” certain regulatory interactions from the previous cell cycle, enabling a continuity of gene regulation across cell generations. The team observed that these loops tend to localize near genes that exhibit transcriptional spikes late in mitosis, suggesting a potential link between structural persistence and transient transcription during division.
Implications for gene regulation and cell identity
The findings bridge a long-standing gap between 3D genome architecture and functional gene expression. By demonstrating that fine-scale regulatory loops survive mitosis and can influence transcriptional timing, the study provides a plausible mechanism for how cells consistently regulate gene activity across divisions. This challenges the notion of a complete structural reset each cell cycle and hints at a more nuanced model of genomic memory.
What researchers are pursuing next
Hansen, Banigan, and colleagues plan to explore how cell size and shape influence microcompartment formation, and how the cell decides which microcompartments to retain after mitosis. Understanding these decisions could illuminate how errors in genome architecture contribute to disease and aging, and may guide strategies to modulate gene expression in medical contexts.
Context and collaboration
The study, published in Nature Structural and Molecular Biology, is led by MIT researchers with contributions from scientists at the University of Pennsylvania and Weill Cornell Medicine. The work underscores the value of ultra-high-resolution mapping in revealing subtle, functionally meaningful genome organization previously hidden by less precise techniques.
Why this changes our view of the genome
By showing that structure and function persist in mitosis, the study reframes how biologists think about the genome’s 3D organization as an active participant in cell division, not a passive remnant. The persistence of microcompartments offers a plausible explanation for early mitotic transcription spikes and opens new avenues for studying how cells preserve identity across divisions.
