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Scientists Map DNA Sequences that Control Genes

By Edward R. Winstead

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Yeast

Scanning electron micrograph of the yeast S. cerevisiae.
Scientists have for the first time searched the entire genome of an organism and come up with a nearly comprehensive list of short DNA sequences involved in switching genes on and off.

The work was done in yeast by researchers who are hoping, eventually, to understand how genes are regulated in the human body and what happens when genes are not regulated properly, including how problems with the regulation of genes leads to diseases such as cancer and diabetes.

With the sequencing of the human genome complete, the next big challenge for biologists is to work out the details of how genes are regulated, says Ernest Fraenkel of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and a leader of the new study along with his colleague Richard A. Young.

“We have a list of human genes and we need to figure out how the genes are used,” Fraenkel says. The goal is to identify the DNA sequences that regulate every human gene and learn when they’re used in the different tissues of the body.

In the yeast study, the researchers identified 203 DNA sequences that regulate genes (the human genome may have ten times this number). They also tracked the regulation of genes as yeast was grown in different environments, which, as expected, showed that genes are regulated differently depending on a cell’s needs. The findings appear in Nature.

An example of how information about the regulation of genes can be important to understanding human diseases came earlier this year in a study by these researchers and their colleagues. Using the same methods, they identified a gene that, when mutated, alters the regulation of many genes in the liver and the pancreas.

The researchers concluded that the gene, HNF4α, is a potential risk factor for type 2 diabetes. The findings appeared in Science in February 2004.

“As we’re working on these tools in yeast, we always have our eyes on how they can be used in human studies,” says Fraenkel.

See related GNN story: Diabetes Susceptibility Gene Discovered

Harbison, C.T. et al. Transcriptional regulatory code of a eukaryotic genome. Nature 431, 99-104 (September 2, 2004).
Odom, D.T. et al. Control of pancreas and liver gene expression by HNF transcription factors. Science 303, 1378-1381 (February 27, 2004).

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