"We may get several thousand sets of such measurements over the course of a single experiment," said DiMaggio.
When seemingly similar histones are broken into small fragments, differences in the locations of modifications become more apparent. The computer algorithm -- based on an area of math called integer linear optimization -- repeatedly compares all the fragments until it produces a highly accurate list of modifications and their locations.
"To see separation of nearly identical species and identify and quantify them with high confidence is very exciting," said Young. He also noted that of the many millions of combinations of modifications possible only a few hundred actually appear in real human cells. This observation implies that combinations of these relatively few modifications form a code that can now be deciphered.
The next step will be to link specific patterns of modifications with observable changes in cells. For example, when normal cells transform themselves into cancerous cells, scientists could track the corresponding changes in the histones. Similarly, scientists could identify particular histone codes that are required for stem cells to change into specific tissue types, such as nerve cells or insulin-producing cells. Understanding and potentially reprogramming these processes could have important implications for regenerative medicine, cancer and other diseases.
As a start, the researchers are collaborating with biologists from the University of California- Los Angeles to identify histone codes relevant for stem cell behavior. "We've shown we can measure modified histone forms, but there's so much to do now," said Garcia. "This is really the beginning of some true biological breakthroughs."
|Contact: Steven Schultz|
Princeton University, Engineering School