The genomes master switches are DNA-binding proteins called gene activators. In humans, there are about a 1000 such activators controlling important functions in life, including cell growth and development. Some of the best known of these switchesthe p53 protein, for exampleare those that play a role in cancer. Others play a role during development, designating which cells become nerve or muscle cells, for instance. Scientists know the identity of nearly 600 master switches and know the function of at least 250 of them; their hope always has been to find the set of all genes they control so that they could crack open the genetic basis of health and disease.

However, finding all the genesi.e., the circuitrydirectly controlled by any given master switch has been a painstakingly long and tedious process, involving years of biochemical and molecular experiments. The new technique reported in Science provides a way to get the data in a global fashion and will allow researchers to do in a week what would have taken years to achieve.

"Our technique could conceivably be used in human cells to create a map matching up the master switches with the circuits they control," says Bing Ren, a postdoc in the Young lab.

Although DNA arrays are useful in determining a cells expression profile (a snapshot of which genes are turned on and off in a cell) they represent an overall picture and capture the cells state at a moment in time. One perturbation in the environment or a slight change in the tumor could trigger a cascade of changes, all of which are captured in the snapshot. Such information is invaluable to researchers, but when it comes to identifying the one crucial master switch, finding it from DNA arrays can be like finding a needle in the haystack.

In this study, the Young lab scientists creat
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Contact: Nadia Halim
halim@wi.mit.edu
617-258-7270
Whitehead Institute for Biomedical Research
20-Dec-2000