Frank Pugh, associate professor of biochemistry and molecular biology, recently discovered that genes do not function purely on a stress-triggered response system. Instead, it was found that genes are regulated in two ways.

Some genes are regulated according to prevalent environmental stresses such as hunger and heat, whereas others are regulated on a less extreme basis. Pugh and his associates' studies on the discovery of gene regulation bipolarity were published in the March 5 edition of the journal Cell and the February 27 edition of Molecular Cell.

Pugh's studies at Penn State over the past 12 years have revolved around gene regulation and how genes control bodily processes. Pugh's study of gene regulation in yeast cells, which led to the discovery of gene bipolarity, began two years ago.

"In the average human cell, there are 30,000 control genes," he said.

To simplify the study of gene regulation, Pugh and his students and colleagues study simple yeast cells.

"Like human cells, yeast cells turn certain genes on and off in response to certain stimuli.

"Our general understanding before was that it wasn't understood whether every gene is turned on or off in a different way. How basic regulations function were largely unknown," Pugh said. "We found that there are two extreme behaviors -- hence the 'bipolar' behavior."

The first is the gene's response to stress, such as UV light, an infection or hunger.

"These genes are more likely to respond to stresses related to the environment. The common misconception is that these genes are representative of how all genes are
regulated in an organism," he said.

The second kind of gene that Pugh discovered in his studies was what he referred to as "housekeeping genes." In their research, Pugh and his associates found evidence that these so-called housekeeping functions do not need to be regulated to the extent that stress-related functions do.

"Housekeeping functions are turned off and on a more regular basis," Pugh said.

In his studies of gene regulation in yeast cells, Pugh found that most proteins are regulated by genes that respond to housekeeping functions, while only a select few genes are regulated by cell for stress related functions.

"Ninety percent of genes fall into the housekeeping function," he said. "It is important, however, to establish that the gene regulation isn't black and white. Regulation occurs more along a continuum, but the difference between the stress-triggered genes and the housekeeping genes is important.

"We've been working on this study for about two years. Historically, we have only studied one gene at a time. However, what was different about this study is that we used DNA microarray technology that allows us to view thousands of genes at a time," Pugh said.

He also said only genes that underwent really exciting regulation were studied extensively before the DNA microarray technology. Now, with the technology, the regulation of all the genes within an organism can be studied simultaneously.

Graduate students Andrew Basehoar and Kathryn Huisinga and senior research technologist Sara Zanton assisted Pugh in the research.

Huisinga worked primarily with the microarray research, and Zanton worked with transcription factor binding.

"I've been working very hard to get good data to submit to the Cell for the past four months," Zanton said.

Specifically, Zanton researched chromatin immunoprecipitation, also known as a protein-binding assay or test. "I basically looked for where certain proteins bind," she said.

Getting the assay to work in the way they wanted and on a consistent basis was a problem at first.

"There was a lot of data that was difficult to find real relationships with, but after a while, it got easier. I'm continuing the technique now with other proteins," she said.