Pulling the strings of our genetic puppetmasters

IMAGE:This is Charles Gersbach, assistant professor of biomedical engineering at Duke University. view more

DURHAM, N.C. -- Duke researchers have developed a new method to precisely control when genes are turned on and active.

The new technology allows researchers to turn on specific gene promoters and enhancers -- pieces of the genome that control gene activity -- by chemically manipulating proteins that package DNA. This web of biomolecules that supports and controls gene activity is known as the epigenome.

The researchers say having the ability to steer the epigenome will help them explore the roles that particular promoters and enhancers play in cell fate or the risk for genetic disease and it could provide a new avenue for gene therapies and guiding stem cell differentiation.

The study appears online April 6 in Nature Biotechnology.

"The epigenome is everything associated with the genome other than the actual genetic sequence, and is just as important as our DNA in determining cell function in healthy and diseased conditions," said Charles Gersbach, assistant professor of biomedical engineering at Duke. "That becomes immediately obvious when you consider that we have over 200 cell types, and yet the DNA in each is virtually the same. The epigenome determines which genes each cell activates and to what degree."

This genetic puppetmaster consists of DNA packaging proteins called histones and a host of chemical modifications -- either to these histones or the DNA itself -- that help determine whether a gene is on or off.

But Gersbach's team didn't have to modify the genes themselves to gain some control.

"Next to every gene is a DNA sequence called a promoter that controls its activity," explained Gersbach. "But there's also many other pieces of the genome called enhancers that aren't next to any genes at all, and yet they play a critical role in influencing gene activity too."

Timothy Reddy, assistant professor of biostatistics and bioinformatics at Duke, has spent the better part of a decade mapping millions of these enhancers across the human genome. There has not, however, been a good way to find out exactly what each one does. An enhancer might affect a gene next door or several genes across the genome -- or maybe none at all.

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Pulling the strings of our genetic puppetmasters