What the research is about
DNA can be thought of as a vast library that stores all genetic information. Cells do not use this information all at once. Instead, they copy only the necessary parts into RNA, which is then used to produce proteins-the essential building blocks of life. This copying process is called transcription, and it is carried out by a molecule known as RNA polymerase II.
When RNA polymerase II begins actively transcribing DNA, a specific site called Ser2 on its tail region is marked with a small chemical group known as a phosphate. This phosphate acts as a sign that transcription is in progress. Until now, observing this sign required stopping cellular activity and chemically treating the cells to visualize the phosphate. As a result, it was impossible to see how transcription changes dynamically in living cells.
To overcome this limitation, a research team led by Professor Hiroshi Kimura at Institute of Science Tokyo (Science Tokyo) chose a different approach. Instead of freezing cells at a single moment, they aimed to track transcription continuously without stopping cellular activity.
The team focused on a fluorescent protein called a "mintbody," which was developed from an antibody that binds specifically to the phosphate marker that appears only during active transcription. Professor Kimura and his colleagues succeeded in creating a mouse that expresses this mintbody throughout its entire body. As a result, they became the first in the world to directly visualize sites of active transcription in cells inside a living mouse.
Why this matters
Like countless lights flickering in a dark room, transcription is constantly taking place inside the cell nucleus. Using the mintbody mouse, the researchers observed hundreds to thousands of glowing dots-representing actively working RNA polymerase II-in nearly all tissues, including the brain, liver, and kidneys.
Interestingly, the number of glowing spots varied greatly depending on the cell type. For example, T cells, a type of immune cell involved in defending the body against viruses and abnormal cells, showed many bright signals. In contrast, neutrophils, another type of immune cell, displayed far fewer. These differences clearly reflect how actively each cell type transcribes genetic information according to its role.
The researchers also observed that transcription is highly active in developing and differentiating cells, while it becomes much more stable in fully mature cells. In the testes, they were able to track dynamic transcriptional changes all the way to the stage where transcription nearly stops during sperm formation.
What's next
This technology provides a powerful new tool for understanding fundamental biological processes such as development and cell differentiation. By combining this mouse with disease models-such as those for cancer or aging-researchers can directly observe how transcription differs between healthy and diseased cells.
In addition, this approach may serve as a new way to evaluate how drugs affect transcription, opening the door to applications in drug discovery and immunology research.
Comment from the researcher
Until now, most studies of transcription have focused on cultured cells. This research revealed that transcription in living tissues is far more diverse than we expected. Being able to directly observe genes at work allows us to capture concrete images of life processes that were previously inaccessible. Because this technology can be applied to many organisms, we believe it will greatly advance future research on transcription and gene expression.
（Hiroshi Kimura：Professor, Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo）
