Overview: A surprise in the mitotic genome
For decades, scientists believed that as cells prepare to divide, their chromosomes condense into a tightly packed, featureless slate. Once division finished, the genome would gradually reestablish its complex 3D structure to regulate which genes are active in each daughter cell. A groundbreaking study from MIT challenges this long-standing view, showing that tiny, highly connected genome loops—dubbed microcompartments—persist, and even intensify, during mitosis.
How higher-resolution mapping changed the picture
The MIT team used Region-Capture Micro-C (RC-MC), a high-resolution genome-mapping technique, to examine chromatin architecture with dramatically finer detail than traditional methods. RC-MC focuses on small genome fragments and targeted regions, enabling researchers to detect subtle interactions between regulatory elements and genes that were previously invisible. This approach uncovered a novel class of structures called microcompartments, formed when enhancers and promoters near one another interact and bind tightly in 3D space.
The surprising persistence of microcompartments during mitosis
During mitosis, chromosomes condense to ensure accurate segregation, and larger genome features such as A/B compartments and topologically associating domains (TADs) were known to disappear. The MIT study confirms this loss of broad organization but makes a striking discovery: microcompartments survive, and in fact become more prominent as the cell advances through division. These tiny loops connect regulatory elements and genes even when the genome is most compacted.
Why this matters for gene regulation
The presence of microcompartments during mitosis provides a potential mechanism for how cells “remember” regulatory interactions from one cell cycle to the next. As chromosomes condense, compaction brings enhancers and promoters into closer contact, facilitating microcompartment formation. Once cells exit mitosis and enter G1, many of these loops weaken or disappear, suggesting a dynamic but memory-linked system rather than a complete reset.
Connecting structure to function: a long-standing question
“What we see is that there’s always structure. It never goes away,” says MIT Associate Professor Anders Sejr Hansen. The study helps bridge the gap between 3D genome organization and gene activity, shedding light on how regulatory networks survive the disruptive mitotic process. Co-senior author Edward Banigan and others contributed to a work that positions microcompartments as a key, fine-scale mechanism by which cells regulate transcription across cell cycles.
Implications for biology and medicine
By revealing that microcompartments are maintained or strengthened during mitosis, the findings offer new angles for understanding transcriptional spikes observed near the end of mitosis. Research in the 1960s and later suggested that transcription largely halts during division, with brief resurgences as cells re-enter interphase. The MIT results imply that residual regulatory loops may prime genes for rapid reactivation, influencing how scientists study cell-cycle dynamics and gene expression timing.
Future directions
The team plans to investigate what determines which microcompartments are retained into G1 and how cell size and shape influence 3D genome organization during division. Understanding these rules could illuminate why some regulatory interactions persist across cycles while others are discarded, with potential implications for development and cancer biology where cell-cycle control is disrupted.
Funding for the work came from the NIH, NSF, Broad Institute’s Gene Regulation Observatory, Pew-Steward Scholar Award for Cancer Research, and other supports, underscoring the collaborative effort to map the genome’s hidden architecture at unprecedented resolution.
