Scientists Uncover Persistent 3D Loops in Cell Division Process

In a groundbreaking study, researchers at the Massachusetts Institute of Technology (MIT) have discovered that tiny 3D loops in the genomes of dividing cells persist during cell division, challenging long-held beliefs about the genetic architecture during mitosis. Traditionally, scientists thought that the genome loses its distinctive 3D structure during this critical process, leading to a reset in gene activity. However, this new research reveals that small loops connecting regulatory elements and genes remain intact, offering fresh insights into how genes are regulated.

The study, led by Anders Sejr Hansen, an associate professor of biological engineering at MIT, utilized a novel genome mapping technique with unprecedented resolution. This approach allowed the research team to observe that these 3D loops not only endure but actually strengthen as chromosomes become more compact in preparation for cell division. “This study really helps to clarify how we should think about mitosis,” Hansen stated. “In the past, mitosis was thought of as a blank slate. Now we know that structure is always present; it never goes away.”

### New Insights into Genome Structure

The research team employed a technique known as Region-Capture Micro-C (RC-MC), which provides 100 to 1,000 times greater resolution than previous methods. This advancement enables researchers to analyze specific genome regions in detail, revealing previously unseen structures they termed “microcompartments.” These microcompartments form when enhancers, short sequences of DNA that activate gene transcription, stick together with nearby promoters.

Historically, scientists have mapped 3D genome structures using techniques like Hi-C, which, while effective, lacked the resolution to pinpoint intricate interactions between genes and their regulatory elements. With the RC-MC technique, Hansen and his colleagues could track these structures throughout cell division, leading to surprising findings about their persistence during mitosis.

### A Shift in Understanding Gene Regulation

During mitosis, it was believed that gene transcription halted completely. However, the MIT study suggests that a brief spike in transcription occurs towards the end of this phase. The researchers noted that the microcompartments were frequently located near genes that experience this spike in activity. As chromosomes compact, enhancers and promoters come closer together, facilitating the formation of these loops. Once established, they may inadvertently activate gene transcription before being suppressed as the cell completes its division.

“This transcriptional spiking in mitosis seems like an undesirable accident, arising from the conditions that favor microcompartment formation,” Hansen explained. “The cell quickly prunes those loops when it enters G1, ensuring fidelity in gene expression.”

### Implications for Future Research

The findings from this study open new avenues for understanding the relationship between genome structure and function, particularly in the context of how cells remember interactions across cell cycles. The research team, which included lead author Viraat Goel and senior authors Edward Banigan and others, emphasized the importance of these insights for the field of gene regulation.

Hansen expressed interest in exploring how variations in cell size and shape might influence genome structure. “We’re looking at biological scenarios where cells change shape and size, and how that could explain some 3D genome changes,” he noted.

The research received funding from various organizations, including the National Institutes of Health and the National Science Foundation, highlighting its significance in advancing the understanding of cellular biology. The full study appears in the prestigious journal Nature Structural and Molecular Biology, marking a pivotal moment in the exploration of genomic organization during cell division.