Light Used to Switch on Gene Expression

A new method that uses light-activated molecules to turn gene expression on and off provides greater precision for studying gene function and could lead to targeted therapies for diseases like cancer.

The most commonly used molecules, triplex-forming oligonucleotides (TFOs), can prevent gene transcription by binding to double-stranded DNA, but this process is not precisely controlled.

Now Dr. Alex Deiters, a chemist at North Carolina State University, has found a way to control the TFOs and, by extension, the transcription of certain genes. He attached a light-activated “cage” to a TFO; when exposed to UV light, the cage is removed, and the TFO is free to bind with DNA, inhibiting transcription of the gene of interest.

“In the absence of light, transcription activity is 100 percent," Deiters said. "When we turn on the light, we can take it down to about 25 percent, which is a significant reduction in gene expression.”

Deiters has fine-tuned the process by attaching a caged inhibitor strand to the TFO. The molecule behaves normally in the absence of UV light and binds to DNA, preventing gene expression. When exposed to UV light, however, the caged inhibitor activates and stops the TFO from binding with DNA, turning gene transcription on.

“We've created a tool that allows for the light-activation of genetic transcription,” he said. “By giving researchers greater temporal and spatial control over gene expression, we've expanded their ability to study the behavior of particular genes in whichever environment they choose.”

The research, which was funded by the National Institutes of Health, appeared online in ACS Chemical Biology.

For more information, visit: www.ncsu.edu