Mechanics effects gene expression too

I’ve been posting a lot about the complications of genetics, largely as a response to recent criticism about the perceived failure of private and government research investments in genetics to return treatments for disease. My attitude is that there’s been a failure to have realistic expectations about just how complex genetic processes are. I’ve already pointed to articles about “RNA editing” and “epigenetics” and how they affect gene expression.

Now add another factor: gene expression affected by mechanical forces around DNA. Epigenetics and RNA editing are about chemical reactions with DNA or RNA that play a role in determining which genes get turned on or off. But research by U Michigan that’s going to be published in Physical Review Letters has shown that mechanical forces like stretching play a role too.

Scientists understand the chemistry involved in gene expression, but they know little about the physics. The U-M group is believed to be the first to actually demonstrate a mechanical effect at work in this process…

“We have shown that small forces can control the machinery that turns genes on and off. There’s more to gene regulation than biochemistry. We have to look at mechanics too,” said Jens-Christian Meiners, associate professor in the Department of Physics and director of the biophysics program.

We’re all pretty familiar with the idea that DNA forms long helical chains of molecules that resemble a twisted ladder. But this twisted ladder also coils into loops. Proteins acting like buckles connect distant parts of the DNA chain and attach the loops at specific points. These loops and contact points are part of gene expression.

The researchers used “optical tweezers” to stretch out the DNA so that it couldn’t loop back on itself naturally. That threw the normal genetic expression process off. The inside of a cell is an extremely active place with molecules furiously banging into each other all the time. So that brings up a question:

While this experiment was performed on free DNA, the scientists say forces as much as 100 times stronger are regularly created inside cells as contents shift and buffet each other. “If we can basically shut this process down with the tiniest force, how could all these larger forces not have an impact on gene expression?” Milstein said.

Good question; one the researchers are trying to figure out. And it’s one more factor that needs to be taken into account for an in-depth understanding of the how our genes work to make us who we are or to make us sick when they malfunction.

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