Microarrayed for Discovery

University of Texas at Austin professor chips in to determine how genes work with each other

Aug. 28, 2007

Scores of scientists from dozens of institutions gave one percent of the human genome a thorough going over as the start of the Encyclopedia of DNA Elements (ENCODE) project.

The headlines from the results, published in June in Nature, were that there’s a lot more going on in the genome that had been thought. It’s not just that one gene does this and another gene does that. It’s that it seems that genes team up with each other and other factors to get things done.

The project expands on the Human Genome Project, which sequenced the entire DNA of the human genome. ENCODE’s role is to figure out which parts of the genome are functional.

If the genome were an automobile, the Genome project compiled the parts list. Now ENCODE is determining how the parts work together to make the car go.

The University of Texas at Austin connection with ENCODE is Vishy Iyer, an associate professor in the Section of Molecular Genetics and Microbiology and the Center for Systems and Synthetic Biology. He had a $1.4 million grant from the National Institutes for Health for the project.

His work contributed to the Nature paper and to a cover article in Genome Research, which carried more papers from the ENCODE project.

Iyer’s work was aimed at finding what transcriptional regulators targeted. He specifically looked at MYC, an oncogene involved in the development of cancer, and identified where it binds to a gene in the region of the genome on which ENCODE concentrated.

Binding allows the genetic instructions to be transferred so that they can go into action.

Iyer’s lab found that MYC binds at the start of a gene, which had previously been unknown.

As with much in science, the discovery generated more questions than it answered.

“It could be that this oncogene has a much broader role in regulating transcription (copying genetic information) than we suspected,” he said. “But one of the things revealed by the ENCODE project is that there are a few transcription regulators that behave like this.”

Iyer’s lab will continue to investigate.

“The binding is really step one. Now we have to dig deeper,” he said.

The ENCODE project is under the National Human Genome Research Institute, which has recruited scientists around the world to work on it.

“It was much more of a community-based effort so even though it’s a consortium,” Iyer said, “each lab was on its own.”

For the project, Iyer developed a technology that made it easier and faster to find interesting things about what he was looking at.

“We developed a method called STAGE (Sequence Tag Enrichment of Genomic Enrichment) which we used for our ENCODE project to identify targets of gene regulators,” he said. “This technology is based on sequencing signature tags from DNA.”

They also used tiling microarrays to identify the targets.

A tiling microarray is a technology that has developed in the past two or three years, Iyer said. It can process much more information than more conventional microarray technology.

“Tiling simply means that you have a chromosome and you don’t make any assumptions about what’s important and what’s not important, you just start at one end and march right across,” Iyer said. “Every piece of the chromosome is represented on this chip at very high resolution, so then you can do any experiment you want to find out where a regulator binds.”

He and his collaborators have submitted a proposal for the next round of ENCODE work.

For more information, contact: Photos: Marsha Miller