What makes genes stop and go?

MICHIGAN STATE (US) — Knowing how certain proteins are supposed to slow genes during development could explain how some diseases like cancer occur when those genes are unable to shift gears properly and can’t stop.

The binding of repressor proteins to DNA provides a molecular switch for such regulation, says David Arnosti, professor of molecular biology at Michigan State University.

Although the two types of protein have been identified as silencers of gene expression, each one uses a distinct molecular mechanism to halt the process.

Details of the research are published in Current Biology.

“In automotive terms, a driver can either brake or downshift the transmission to achieve the same result,” Arnosti says. “Similarly, short-range and long-range repressor proteins both interfere with the basic gene expression machinery, but in different ways.”

In sequencing the human genome, scientists have assembled a parts list and can point to genes that play a part in diseases.

Arnosti’s research shows how these genes are regulated through special mechanisms, controlling an entire organism’s genes.

“Mechanistic studies such as this are giving us the assembly instructions for the genome,” Arnosti says. “Basically, it’s giving us a way to read genomic control instructions.”

The research involves fruit flies, which are genetically similar to humans, so could soon lead to advances in human medicine, Arnosti says.

“We like to say that fruit flies are like little people with wings; they have the same basic genetic nuts and bolts, including genetic switches and proteins.

“While our work is the first of its kind, it is only a small step for other scientists to begin conducting these same studies on human genes. With regards to disease, this study gives us the basic tools to look at genes in a disease state and understand what is going wrong at the genetic level.”

Arnosti’s research furthers the work of researchers using molecular approaches to understand mechanisms of gene regulation. One area the group is promoting is integrated systems biology studies.

“By taking a systems biology approach, we’re beginning to understand that it’s not one bad gene that’s responsible for causing cancer,” Arnosti says. “We are starting to unravel how gene switches talk with one another as well as how a number of slightly defective genes interact to create a diseased state.”

Arnosti’s work is funded in part by the National Institutes of Health.

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