Slowing Down Developmental Genes

There’s more than one way to silence gene activity, according to new research.

Downregulating activity is how healthy genes should shift out of their development cycle. The findings, which are published in Current Biology, discuss how specific repressor proteins slow genes during development and how the process is comparable to slowing down a car, according to David Arnosti, PhD, director of Michigan State University’s Gene Expression in Disease Development initiative.

The binding of repressor proteins to DNA provides a molecular switch for such regulation. 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, said Arnosti in a press release.

These mechanisms may hold the keys to explaining how diseases, such as cancer, diabetes, and arthritis can be traced to genes that are unable to shift gears properly and can’t stop.

“In automotive terms, a driver can either brake or downshift the transmission to achieve the same result,” said Arnosti, who published the paper with Li M. Li, a former MSU doctoral student now working at the University of California, Berkeley. “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 disease. Through Li’s and Arnosti’s research, however, scientists can now begin to see how these genes are regulated through special mechanisms, helping show how an entire organism’s genes are controlled.

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

Arnosti’s research involved fruit flies, which have more genetic similarities to humans than was once thought. Based on these similarities, the team’s research could soon lead to advances in human medicine.

Fruit flies, according to Arnosti, “have the same basic genetic nuts and bolts” as humans, 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, he said.

MSU researchers are using cutting-edge molecular approaches to understand mechanisms of gene regulation and promote excellence in training the next generation of biological researchers. One area that 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 said. “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.”