Kanazawa University Research: Visualizing the Mechanics of Hormone-Driven Gene Activation: Insights into Breast Cancer

KANAZAWA, Japan, April 23, 2025 /PRNewswire/ -- Scientists at Nano Life Science Institute (WPI-NanoLSI), Kanazawa University have captured real-time footage showing how a key hormone receptor activates genes, offering a clearer view into one of the most fundamental Kaprocesses in biology.

Using high-speed atomic force microscopy (HS-AFM), Richard Wong and colleagues at Kanazawa University directly visualized how the estrogen receptor alpha (ERα) binds to DNA and switches on genes in response to the hormone estrogen. Their findings, published in ACS Nano, reveal new molecular details of hormone signaling, with important implications for diseases like breast cancer.

Key Points

• Researchers used high-speed atomic force microscopy (HS-AFM) to directly film how estrogen receptor alpha (ERα) binds to DNA in living-like conditions.
• Estrogen binding improves ERα's ability to dimerize and accurately target specific DNA sites called estrogen response elements (EREs).
• Findings support a new 'Ligand-Induced Dimerization (LID)' model and offer insights into hormone-driven diseases like breast cancer.

Estrogen receptors play a critical role in controlling gene activity in many tissues. When estrogen binds to ERα, the protein changes shape, forms a dimer (a molecular pair), and attaches to specific regions of DNA called estrogen response elements (EREs). Although the importance of this process has been known for decades, it had never before been observed unfolding at the single-molecule level in real time.

To capture this, the researchers used HS-AFM to scan individual ERα molecules interacting with DNA. They compared the behavior of ERα with and without estrogen present. Their experiments showed that ERα could bind to DNA without estrogen but did so less precisely and less stably. When estrogen was present, ERα molecules dimerized more efficiently and exhibited targeted, stable binding to ERE sequences.

"Our study shows that estrogen acts like a molecular matchmaker," says Richard Wong. "It not only triggers ERα to find the right DNA sequence but also stabilizes its grip, ensuring accurate gene activation."

Based on these observations, the team proposed a new 'Ligand-Induced Dimerization' (LID) model explaining how hormones fine-tune the dynamic behavior of receptors at the DNA level.

This work provides direct visual evidence of how molecular signals from hormones lead to precise gene control — a fundamental advance that could guide new strategies for treating hormone-driven diseases.

Glossary

• Estrogen receptor alpha (ERα): A protein inside cells that binds estrogen and controls the activity of specific genes.
• High-Speed Atomic Force Microscopy (HS-AFM): An imaging technology that captures the movement of individual molecules in real time.
• Ligand: A molecule, such as estrogen, that binds to a protein and changes its shape or function.
• Dimerization: The process by which two protein molecules join together to form a pair (dimer), often necessary for function.
• Estrogen Response Element (ERE): A specific sequence of DNA that the estrogen receptor recognizes and binds to, controlling gene expression.

Figure: How Estrogen Receptor Binds DNA.

https://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/Eye-catching-imageEN_ACS-Nano_2025.4.23.png

Caption: This illustration shows the estrogen receptor alpha (ERα, in orange) attaching to DNA (in blue) as a pair, or dimer. The image is based on real-time, high-speed atomic force microscopy (HS-AFM) data, showing how ERα recognizes and binds specific DNA sequences to activate genes. The close-up highlights the dimer sitting on the DNA strand — a key step in hormone-driven gene regulation.

Reference

Goro Nishide, Tomoka Ishibashi, Keesiang Lim, Yujia Qiu, Masaharu Hazawa, Ayami Matsushima and Richard W. Wong, Zooming into Gene Activation: Estrogen Receptor α Dimerization and DNA Binding Visualized by High-Speed Atomic Force Microscopy, ACS Nano (2025).

DOI: 10.1021/acsnano.4c14943

URL: https://doi.org/10.1021/acsnano.4c14943

Funding

This work was supported by the World Premier International Research Center Initiative (WPI) and the WISE Program for Nano-Precision Medicine, Science, and Technology of Kanazawa University, funded by MEXT.

Additional support came from MEXT/JSPS KAKENHI (24K18449, 23H00521, 22H05537, 22H02209, 23H04278, 24H01276, 25H02360), JST CREST (JPMJCR22E3), the Hokuriku Bank, SECOM Science and Technology Foundation, Takeda Science Foundation, and Shimadzu Science Foundation.

Contact

Kimie Nishimura (Ms)

Project Planning and Outreach, NanoLSI Administration Office

Nano Life Science Institute, Kanazawa University

Email: nanolsi-office@adm.kanazawa-u.ac.jp

Kakuma-machi, Kanazawa 920-1192, Japan

About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University

Understanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms".

Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale.

https://nanolsi.kanazawa-u.ac.jp/en/

About the World Premier International Research Center Initiative (WPI)

The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

See the latest research news from the centers at the WPI News Portal:

https://www.eurekalert.org/newsportal/WPI

Main WPI program site: www.jsps.go.jp/english/e-toplevel

About Kanazawa University

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

http://www.kanazawa-u.ac.jp/en/