Imagine being able to control genetic expression by flipping
a light switch. Researchers at North
Carolina State University are using light-activated
molecules to turn gene expression on and off. Their method enables greater
precision when studying gene function, and could lead to targeted therapies for
diseases like cancer.
Triplex-forming oligonucleotides (TFOs) are commonly used
molecules that can prevent gene transcription by binding to double-stranded
DNA. NC State chemist Dr.
Alex Deiters wanted to find a way to more precisely control TFOs, and by
extension, the transcription of certain genes. So Deiters attached a
light-activated “cage” to a TFO. When exposed to ultraviolet (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,” says Deiters. “When we turn on the light, we can take it down to
about 25 percent, which is a significant reduction in gene expression.”
Additionally, Deiters fine-tuned the process by attaching a
caged inhibitor strand to the TFO. In the absence of UV light, the TFO behaves
normally, binding to DNA and preventing gene expression. However, when exposed
to UV light, 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,” Deiters says. “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 appears online in ACS Chemical Biology, and was funded by the National
Institutes of Health. Deiters worked with NC State graduate students Jeane M.
Govan, Rajendra Uprety and James Hemphill and Wake Forest
University’s Mark O.
Lively on the research.
