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Turned-On Genes
Scientists learn more about gene regulators
By Lisa Scanlon

Although scientists finished a draft sequence of the human genome four years ago, little is known about how genes get called into action. Now, however, researchers at MIT and the Whitehead Institute for Biomedical Research have begun to fill in the missing information: they have found all of the regulatory sequences in the yeast genome.

Regulatory sequences are specific parts of the genome that turn genes on and off by interacting with molecules called gene regulators. By locating these regulatory elements and thereby determining where regulators bind to the genome, scientists can deduce the regulators’ functions. The team of investigators, led by Whitehead researchers Richard Young and Ernest Fraenkel, PhD ’98, and MIT computer scientist David Gifford ’76, is particularly interested in regulators because mutated versions of them are associated with many diseases, including diabetes and cancer.

Previously, it could take years to find a regu­lator’s binding site. The MIT and Whitehead researchers developed a method to speed up the process. First they found the binding sites’ rough locations: they placed regulators on chips containing thousands of pieces of DNA and observed where they bound. Then, by using computer algorithms to compare these data with data from other yeast species, the researchers were able to identify precise binding locations. If the sequence for a potential binding site in one species of yeast exists in several other yeast species, then “it means it’s probably important for something,” and is most likely a controlling element, says Chris Harbison, a Whitehead graduate student who worked on the project. The researchers also placed cells in a dozen different environments to reveal binding locations that are only used under certain conditions.

Though the human genome is far larger and more complex than the yeast genome, researchers at Whitehead and MIT are already applying these technologies to understanding human genetics.