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Researchers Repress DNA Loop Formation by Applying a Small Force


Researchers at the University of Michigan have shown that entropic -forces as small as 100 femtonewtons are capable of altering gene expression. By applying force to DNA tethered to a microscope slide using optical tweezers optimized in their lab, Joshua Milstein says that he and his team were able to effectively slow the rate at which DNA loops were formed by 10-fold.

To demonstrate the intricacy of their experimental manipulation, Milstein offered a relative sense of scale. "It takes about a newton of force to hold a cup of coffee. If you take a millionth of that, and then divide by another million, you get a piconewton," he says. "A femtonewton is 1,000 times smaller than that."

The Michigan team used a strictly quantitative approach in their methods and analyses. Based on previous studies, which had hypothesized that if tension was added to a strand of DNA it would be possible to prevent the formation of loops, Milstein and his colleagues developed a formula that could assign — based upon the amount of force with which the DNA was "pulled" — a numerical value for the rate at which loops form.

Current estimates surmise that it takes about 100 femtonewtons of force to drive loop formation. When DNA loops back over and on top of itself, it prevents the genes from within the loops from being expressed. The scientists were surprised to find that their experimental data had fit their predictions so well; however, further investigations are needed.

Milstein says that because the biological forces acting within the cell are predicted to be on the order of tens of piconewtons, and DNA looping is controlled by a force estimated at less than one-hundredth of that, there must be other factors that come into play. "A natural question, then, is to ask if the cell accounts for the effects of tension so that it can [still] reliably control the expression of genes," he says.

In the future, the team members hope to be able to observe loop formation within living cells, and they're developing techniques to do so using nanoparticle labels and "clever" microscopy.

"Truly quantitative results such as the one we reported are still rather sparse throughout biology," Milstein says. "But they're all important because of their predictive power."