Scientists produce the scrip...( lled genome-wide location analysis dev...)

The method is based on DNA microarray technology, which displays ordered segments of DNA and provides researchers with a compact format to quickly analyze how proteins interact with the DNA of an entire genome.

Of the 141 transcription factors known for baker's yeast, Young and his colleagues observed that 106 bound to about 2,300 locations in the genome, representing about 37 percent of the yeast's known genes. The picture is complex, because a transcription factor can bind to more than one gene, and one gene can bind more than one transcription factor.

The remaining 35 transcription factors were undetectable under current experimental conditions. Many of the other genes come into play under less typical environmental conditions (such as heat), interactions the group is now studying. In addition, some protein-gene binding events were eliminated by the group's stringent statistical requirements.

Whereas earlier work required approximately 300 researcher-years to find just some of the binding sites of only one transcription factor (Gal4), the present experiment needed only about a researcher-week for each of the yeast's hundred-some regulatory proteins. "Without this increase in productivity, we just wouldn't be able to create a comprehensive view of the how the genes in the cell are controlled," Young says.

Missed Cues Lead to Disease

The result is a vast network of the interactions between proteins and genes, a complex script that specifies the roles of all the players involved in a cell's life. Each transcription factor was tied to a group of "supporting actors" it controlled--additional genes involved in cell growth, metabolism, or environmental response. Often times, the various transcription factors would cue each other to make more or less transcription factor, tying togeth
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Contact: Nadia Halim
halim@wi.mit.edu
617-258-9183
Whitehead Institute for Biomedical Research
24-Oct-2002