All brain cells are the same, genetically speaking. Yet somehow they play vastly different roles, some directing movement, others participating in language or thought. Now, a study finds that a chemical known to turn genes on and off may be partially responsible for this division of labor. The results, researchers suggest, could help scientists better understand psychiatric and neurological diseases.
It takes more than genes to make people who they are. Identical twins, for example, can look and act differently even though they share the same DNA (ScienceNOW, 5 July 2005). Environmental factors likely contribute to this variation, but it also seems to depend on so-called epigenetic phenomena, activity that regulates genes without changing the DNA code (ScienceNOW, 12 April 2006). In the 1960s, researchers found that the addition of a molecule called a methyl group to cytosine, one of the four building blocks of DNA, could turn off genes. Since then, scientists have found that this process, called methylation, can also turn genes on and that it is linked to cancer (ScienceNOW, 31 January 2000) and short-term memory formation (ScienceNOW, 14 March).
Because no studies have surveyed methylation's role in assigning marching orders to brain cells, geneticist Andrew Feinberg and psychiatric neuroscientist James Potash, both of Johns Hopkins University in Baltimore, Maryland, decided to investigate. Along with their colleagues, they compared possible methylation sites on 807 genes in 76 samples from human brains. Among the regions studied were the cerebellum, which controls movement, and the cerebral cortex, which controls language and memory. The team found that methylation patterns differed by brain region, indicating that epigenetics helps divide up the brain's functions. These patterns proved more robust than differences in methylation linked to race, age, or sex, the team reports in the December issue of The American Journal of Human Genetics.
The study makes clear, Feinberg says, that "working on the brain without thinking about epigenetics is like working with a blindfold on." By understanding normal methylation, he adds, researchers can begin to look at methylation gone wrong, possibly in autism, depression, bipolar disease, and schizophrenia.
Given that epigenetics has been shown to modify gene expression in other parts of the body, the brain results are not surprising, says psychiatrist Schahram Akbarian of the University of Massachusetts Medical School in Worcester. "One could say neuroscience is catching up with the rest of the field."