Despite carrying identical DNA, all cells in a body aren't identical -- a cell in the kidney looks and functions very differently from one in the brain. What makes this specialization possible is a set of instructions stored outside of genes or DNA -- "epigenetic" information -- that helps each cell adapt to its context. Key players in this process are histones, tiny protein spindles that the 6-foot-long DNA molecule wraps itself around in forming a chromosome.
Scientists have long known that histones acquire a variety of small chemical decorations -- small molecules attached here and there along the length of the histone. The type and location of these add-ons can regulate nearby genes. Single modifications are known to turn genes on or off, but what happens when multiple modifications occur in combinations -- the "histone code" -- remains a mystery.
"The ability to understand this phenomenon and control it with great precision would be revolutionary to medicine," said Young.
Distinguishing between various modified forms of a histone has been challenging because several combinations of different modifications can have nearly the same mass. Indeed, under conventional tests two histones with very different functions could appear identical if they have the same set of modifications but at different locations on the molecule. Before now, efforts to distinguish such subtle differences were extremely difficult and time consuming. "We have now developed the first practical means to do this," said Young.
The Princeton team combined physical, chemical and mathematical techniques for separating one histone variation from another. First they passed a mix of various histones through a very thin, long tube containing a specially designed material that causes different histone forms to emerge from the tube at different times over a two- to three-hour
|Contact: Steven Schultz|
Princeton University, Engineering School