New research sheds new light on the process of methylation in DNA.
Researchers zoomed in on the question: if the genetic information is the same in all cells, as it should be, why do muscle cells look and act differently than skin cells?
“This study won’t immediately lead to a new drug, but it provides one more step toward more rational drug design…”
“To selectively turn on and off different genes to determine the cell type, you need to modify this gene expression, and one way to do that is to chemically modify DNA,” says Wonmuk Hwang, associate professor in the biomedical engineering department at Texas A&M University.
A major way the body achieves this is through methylation, where methyl groups stick to a particular location in DNA, so that the group blocks the cell from reading the genetic information in this region.
In addition, methylation affects local flexibility of DNA, which in turn controls how DNAs are packaged into chromosomes. While scientists have generally understood the outlines of these processes, how methylation affects DNA’s mechanical properties has remained unknown.
Through extensive simulations using supercomputers, the researchers determined how the areas of DNA around the methyl groups bump against each other and alter mechanical behaviors.
Along with that discovery, Hwang says they found another unexpected insight.
“These methyl groups not only bump against neighboring atoms in DNA, but water molecules rearrange around these methyl groups,” Hwang says. “The rearranged water molecules actually resist deformation even in the absence of the direct collision of atoms with the methyl groups, as if the surrounding water molecules are a part of DNA itself.”
There are multiple applications to understanding how processes such as methylation work. One example Hwang gives is developing more knowledge on how cancer cells function.
“Cancer cells often methylate their DNA to turn off genes that control cell division, promoting uncontrolled growth,” he says.
Another is drug interaction with DNA and how drug design should take these water molecules into account.
“This study won’t immediately lead to a new drug, but it provides one more step toward more rational drug design,” Hwang says. “People have been working on cancer for decades, and I don’t claim that I can solve the problem right away. But all of these efforts make step-by-step progress in the right direction.”
Hwang says the method his team developed opens the door to analyzing other types of DNA or RNA modifications and how their behavior changes depending on what drugs researchers introduce.
The research appears in Biophysical Journal.
Source: Jennifer Reiley for Texas A&M University