In an unexpected twist to what we know about cellular mechanics, researchers at MIT have stumbled upon a phenomenon that could reshape our understanding of how genes are regulated during cell division. A team led by Anders Sejr Hansen, an associate professor of biological engineering at MIT, employed a cutting-edge genome mapping technique to reveal that contrary to prior beliefs, small but significant structures within our genome endure the process of mitosis. Hansen explained, "What we see is that there's always structure. It never goes away." This discovery, detailed in a study published in Nature Structural and Molecular Biology, challenges the long-standing idea that the 3D organization of the genome entirely disassembles during cell division, as reported by MIT News.
Previous conceptualizations had suggested that as cells divide, their genomic structure essentially hits the reset button, returning to a rudimentary state before reassembling into a more complex form. However, pioneering work by the MIT scientists, including Viraat Goel, a recent Ph.D. graduate and lead author of the study, have identified "microcompartments" that persist through mitosis. These structures, comprising loops that link regulatory elements and genes, have been found to not only survive cell division but also become more prominent, suggesting a mechanism that helps cells remember which genes were active in the parent cell and thus possibly influencing gene expression in the daughter cells.
Effie Apostolou, an associate professor of molecular biology in medicine at Weill Cornell Medicine, not involved in the study, praised the technique's ability to reveal these microcompartments, stating, "This study leverages the unprecedented genomic resolution of the RC-MC assay to reveal new and surprising aspects of mitotic chromatin organization," as noted by MIT News. With a higher resolution, utilizing the Region-Capture Micro-C (RC-MC) technique, researchers were able to focus on smaller segments of the genome, providing clarity on the highly connected loops that exist between enhancers and promoters, which play crucial roles in gene activation.
The presence of these structures not only adds a layer to the genomic architecture that withstands division but may also explain a puzzling increase in gene transcription observed at the end of mitosis—a phenomenon that has been recognized since the 1960s. According to the MIT study, active genes in the neighborhood of these microcompartments exhibit a marked transcriptional spike that is quickly suppressed until the cell fully completes division. "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 told MIT News. This transcriptional activity perhaps offers the cell a preview of what genetic programs will be expressed immediately following division.
Continuing this line of inquiry, researchers are now considering how other cellular factors, like size and shape, may influence chromosomal compaction and thus the structure and function of these genomic microcompartments. With funding from several prestigious institutions, including the National Institutes of Health and the National Science Foundation, the explorations underway at MIT might soon elucidate how cells ensure the right genes turn on at the right time during the life of a cell and beyond, impacting our understanding of developmental biology and disease progression.
