Bernstein has been studying chromosome wrappings for five years as a postdoctoral researcher in the lab of Stuart Schreiber. Together they worked out techniques to examine the way genes are packaged in yeast. To go from yeast to humans required a technological breakthrough, however.
"Most prior studies involved only single genes, but we wanted to investigate entire chromosomes, which contain hundreds of genes," Bernstein notes.
He and Schreiber enlisted the help of Affymetrix, which makes so-called "gene chips" that rapidly scan millions of small sections of chromosomes to detect gene activity. But the scanning results left them with a huge amount of data, and the daunting task of deciphering what it means in terms of how genes function. For that part of the project, they teamed with investigators from the Broad (pronounced to rhyme with "road") Institute.
"The human genome still has many surprises lurking within it," comments Lander, who is director of the institute. "One of the most important is the mystery of how genes are turned on. The ability to take global views of (chromosome packaging) in human cells holds tremendous promise for unraveling the mystery."
To begin unraveling this mystery, the researchers studied large regions of the genome and identified the DNA sequences associated with chromatin that contains "on" tags. DNA is the same in all the cells in our body. What makes the cells do different jobs is that different genes are turned on. For example, the set of genes turned on in a nerve cell is different from those turned on in muscle, heart, blood, and other cells.
Although the exact ways genes are turned on and off remain unknown, the tags in chromatin are believed to play a major role. Until now, however, it had not even been known which regions of the genome carry such tags.
A complete surprise
Most regions of the chromatin have only a few "on" tags, but in regions packaging cluster