Live Imaging captures DNA folding in sperm cells for the first time

The Nano Life Science Institute (WPI-Nanolsi), Kanazawa University, and fellow researchers achieved breakthroughs to understand sperm DNA packages. Using fast atomic force microscopy (HS-AFM), we captured the real-time process of protamine (PRM)-induced DNA condensation, providing important insights into fertility, genomic stability, and future applications of medicine. Their findings are published in Nucleic Acid Research.

In most cells, DNA is wrapped around a protein called histone, and is loosely packed for gene activity and accessible. However, in sperm cells, histones are replaced by protamine, allowing for extreme DNA condensation. This compression is essential to protect genetic material during fertilization, ensuring efficient transport of DNA into the eggs, and contributing to fertility and embryo development.

Despite its importance, the exact steps in how protamine condenses DNA into a highly stable structure remain unknown. Previous imaging methods allow only static snapshots to be captured, and many questions are not answered. Now for the first time, Richard W. Wong, Kanazawa University, and collaborators at the Nanolife Science Institute (WPI Nanolusi), used real-time imaging to reveal the entire condensation process.

Using HS-AFM, the researchers directly visualized the gradual transformation of DNA structures upon binding to protamine. This study introduces a new card (Coil-Assembly-Rod-Doughnut) model. This explains the condensation process at four different stages of the coil stage where DNA forms a loop loop. The assembly stage in which protamine binds and structural tissue increases. A rod stage where DNA is further compressed. The donut (toroid) stage, the final stable structure is formed.

Furthermore, researchers found that this package was reversible. This means that structures can shift based on environmental conditions. These insights have great implications for understanding male infertility, chromatin biology, and gene therapy.

Fertility research may benefit from insights into DNA packaging and can help diagnose and treat infertility in men. Gene therapy may be improved by a better understanding of DNA compression and its role in genetic material delivery in medical treatment.

Synthetic biology and nanotechnology can also leverage these discoveries to develop new methods for manipulating DNA structures in biotechnology applications.

“Our findings provide a dynamic view of how protamine forms sperm chromatin structures, a process essential for fertility and genome stability,” says corresponding author Wong. “This study not only enhances understanding of reproduction, but also has a wide-ranging impact on genetics and fertility treatment.”