Scientists watch the behavior of a single gene in real time

Scientists at the Albert Einstein College of Medicine of Yeshiva University have observed for the first time that gene expression can occur in the form of discrete "pulses" of gene activity.

The researchers used pioneering microscopy techniques, developed by Dr. Robert Singer and colleagues at Einstein, that for the first time allow scientists to directly watch the behavior of a single gene in real time. Their findings appeared in the current issue of Current Biology.

When a gene is expressed or "turned on," genetic information is transferred from DNA into RNA. This process, known as transcription, is crucial for translating the gene's message into a functional protein. Diseases such as cancer can result when genes turn on at the improper time or in the wrong part of the body.

Researchers customarily use microarrays (also known as "gene chips") to assess gene expression in tumors and other tissues. But with millions of cells involved, microarrays reflect only "average" gene expression. Just how a gene is transcribed in a single cell--continuously, intermittently or some other way--has largely been a mystery.

Now, in observing a gene that plays a major role in how an organism develops, the Einstein researchers observed a phenomenon that until now has been indirectly observed and only in bacteria: pulses of transcription that turn on and off at irregular intervals. Dr. Singer and his co-workers used a fluorescent marker that sticks to the gene only when it is active. Under a microscope, this fluorescent marker appears when the gene turns on, then disappears (gene "off") and then appears again (gene "on").

The focus of the study was a gene important in the life cycle of the social amoeba Dictyostelium, thousands of which sometimes aggregate into a single slug-like mass. This developmental gene plays a major role in transforming the "slug" into a stalk-like structure called a fruiting body, which releases new amoebae.

"The pulsing we observed in this gene would allow it to very precisely regulate development," says Dr. Singer, the study's senior author and professor and co-chair of the Department of Anatomy & Structural Biology at Einstein. He likens a gene to a thermostat:

"Heating a home all the time would be wasteful and would overheat the house," he says. "The solution is a thermostat, which injects a little bit of heat when needed and then turns off. Similarly, a cell needs the gene to be turned on--but too much activity at the wrong time can be a problem, so the solution is to have small bursts of activity."

Still to be discovered, says Dr. Singer, is how the pulsing mechanism itself is controlled. In addition, these findings pertain to developmental genes, which are turned on selectively and only in certain tissues. "Other genes--so-called constitutive genes--are regularly expressed by all the cells of an organism," Dr. Singer notes. "We'd like to find out whether these genes pulse as well."

Also involved in this study were Jonathan R. Chubb (now at University of Dundee in the U.K.), Tatjana Trcek and Shailesh M. Shenoy.

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