Making a botanical breakthrough

SAN DIEGO—A collaboration between researchers at the Salk Institute for Biological Studies and the University of California at Los Angeles has resulted in the capture of the genome-wide DNA methylation pattern of the plant Arabidopsis thaliana—the "laboratory rat" of the plant world—in one sweep.

"In a single experiment we recapitulated 20 years worth of anecdotal findings and then some," says Dr. Joseph Ecker, a professor in the Salk Institute's Plant Biology Laboratory. "Previously, only a handful of plant genes were known to be regulated by methylation. In addition to those, we found hun­dreds of others."

The technological innovations that the team was able to achieve, pioneered by Ecker's team and that of Dr. Steve Jacobsen at UCLA, are expected to have broad impact on the analysis of the human genome, stem cell biology and therapeutic clon­ing. Ecker and Jacobsen were funded by the National Human Genome Research Institute (NHGRI), which launched a public consortium known as ENCODE (Encyclopedia Of DNA Elements).

"There are a number of drug candidates that are directed at DNA methylation," Ecker notes. "This work gives us a more complete view of what changes are happening in cells, whether they are cancer cells, drug-treated cells or otherwise, in terms of their methylation."

The team is now applying the technology used on the plant to a model of colon cancer cells.

The Salk Institute's break­through means a lot for the NHGRI's efforts, because now that the human genome has been sequenced, ENCODE aims to develop technology to decipher what 30 million—just 1 percent—of those genetic letters "spell" by identifying what genes they encode and how epigenetic modifications switch genes off and on.

To do this, the ENCODE proj­ect is encouraging close interac­tions between computational and experimental scientists to evaluate a number of methods for annotat­ing the human genome. By ini­tially concentrating on a limited portion of the human genome, the NHGRI hopes that all of those who have experience and insight into this kind of work will be will­ing to participate, whether or not their approaches are proprietary or have already generated propri­etary data.

Once the goal of deciphering the "spelling" of that 1 percent of the human genome is achieved, the effort will be scaled up to learn more about the dynamics of the whole human genome, the Salk Institute reports, adding that the work of Ecker and Jacobsen may be able to make that possible with a minimum of fuss.