Their findings reveal surprising and previously unknown specifics of how genes get switched on during development of the human body and in diseases such as cancer.
"Each type of cell in our bodies contains the same genes. What makes them do different things involves which genes are turned on," notes Bradley Bernstein, a pathologist at Harvard Medical School. He is also a research associate at the Broad Institute of Harvard and M.I.T., where a complex analysis of packaging of two entire human chromosomes was done for the first time.
Besides Bernstein, the investigators included Morris Loeb Professor of Chemistry Stuart Schreiber; Michael Kamal, Eric Lander, and others at the Broad Institute; and their colleagues from Affymetrix, a California technology company.
The analysis shows a striking and surprising exception in the way some critical genes are activated by the protein packaging. These proteins act like spools for the long strings of DNA that contain our genes and form chromosomes. The researchers studied chemical tags that are attached to the spools and switch on the genes they wrap. In most cases, they found these tags turn genes on and off individually. The big surprise involves clusters of so-called "HOX" genes, which apparently work in concert to control how we develop in the womb. Instead of being activated individually like most genes, the HOX genes appear to be turned on in groups by massive numbers of tags.
HOX genes also are deeply involved in cancer, making the findings particularly important. Some of the proteins that regulate HOX genes are capable of causing or suppressing tumors.