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 visualised how the oestrogen receptor alpha (ERα) binds to DNA and switches on genes in response to the hormone oestrogen.

Their findings, published in ACS Nano, reveal new molecular details of hormone signalling, with important implications for diseases like breast cancer.

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

Oestrogen receptors play a critical role in controlling gene activity in many tissues.

When oestrogen binds to ERα, the protein changes shape, forms a dimer (a molecular pair), and attaches to specific regions of DNA called oestrogen 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 behaviour of ERα with and without oestrogen present.

Their experiments showed that ERα could bind to DNA without oestrogen but did so less precisely and less stably.

When oestrogen was present, ERα molecules dimerized more efficiently and exhibited targeted, stable binding to ERE sequences.

“Our study shows that oestrogen acts like a molecular matchmaker,” says Richard Wong.

“It not only triggers ERα to find the right DNA sequence but also stabilises 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 behaviour 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.

• Oestrogen receptor alpha (ERα): A protein inside cells that binds oestrogen 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 oestrogen, 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.
• Oestrogen Response Element (ERE): A specific sequence of DNA that the oestrogen receptor recognises and binds to, controlling gene expression.

This work was supported by the World Premier International Research Centre Initiative (WPI) and the WISE Programme 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.

Source: Nano Life Science Institute (NanoLSI), Kanazawa University